Author: "Laure Rondi-Reig" - Searchworks@Jio Institute Digital Library Search Results

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84 results on '"Laure Rondi-Reig"'

1. Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice

Author: Allain-Thibeault Ferhat, Elisabeth Verpy, Anne Biton, Benoît Forget, Fabrice De Chaumont, Florian Mueller, Anne-Marie Le Sourd, Sabrina Coqueran, Julien Schmitt, Christelle Rochefort, Laure Rondi-Reig, Aziliz Leboucher, Anne Boland, Bertrand Fin, Jean-François Deleuze, Tobias M. Boeckers, Elodie Ey, and Thomas Bourgeron
Subjects: autism, Shank3, mouse model, stereotyped behavior, striatum compartmentation, GAD65, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Autism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1–2% of patients with autism and intellectual disability, but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterized the behavior of Shank3Δ11/Δ11 mice from 3 to 12 months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEGs). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g., Grm2, Dlgap1), G-protein-signaling pathways (e.g., Gnal, Prkcg1, and Camk2g), as well as excitation/inhibition balance (e.g., Gad2). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs (Cnr1, Gnal, Gad2, and Drd4) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded by Gad2, we showed that the striosome compartment of Shank3Δ11/Δ11 mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of Shank3-deficient mice and strongly suggest, for the first time, that the excessive self-grooming of these mice is related to an imbalance in the striatal striosome and matrix compartments.
Published: 2023
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2. The cerebellum promotes sequential foraging strategies and contributes to the directional modulation of hippocampal place cells

Author: Lu Zhang, Julien Fournier, Mehdi Fallahnezhad, Anne-Lise Paradis, Christelle Rochefort, and Laure Rondi-Reig
Subjects: Biological sciences, Neuroscience, Behavioral neuroscience, Science
Abstract: Summary: The cerebellum contributes to goal-directed navigation abilities and place coding in the hippocampus. Here we investigated its contribution to foraging strategies. We recorded hippocampal neurons in mice with impaired PKC-dependent cerebellar functions (L7-PKCI) and in their littermate controls while they performed a task where they were rewarded for visiting a subset of hidden locations. We found that L7-PKCI and control mice developed different foraging strategies: while control mice repeated spatial sequences to maximize their rewards, L7-PKCI mice persisted to use a random foraging strategy. Sequential foraging was associated with more place cells exhibiting theta-phase precession and theta rate modulation. Recording in the dark showed that PKC-dependent cerebellar functions controlled how self-motion cues contribute to the selectivity of place cells to both position and direction. Thus, the cerebellum contributes to the development of optimal sequential paths during foraging, possibly by controlling how self-motion and theta signals contribute to place cell coding.
Published: 2023
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3. Impaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation

Author: Julie Marie Lefort, Jean Vincent, Lucille Tallot, Frédéric Jarlier, Chris Innocentius De Zeeuw, Laure Rondi-Reig, and Christelle Rochefort
Subjects: Science
Abstract: It is known that Purkinje cell PKC-dependent depression is involved in the stabilization of self-motion based hippocampal representation. Here the authors describe decreased stability of hippocampal place cells based on allocentric cues in mice lacking Purkinje cell PP2B-dependent potentiation.
Published: 2019
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4. Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

Author: Inés González-Calvo, Keerthana Iyer, Mélanie Carquin, Anouar Khayachi, Fernando A Giuliani, Séverine M Sigoillot, Jean Vincent, Martial Séveno, Maxime Veleanu, Sylvana Tahraoui, Mélanie Albert, Oana Vigy, Célia Bosso-Lefèvre, Yann Nadjar, Andréa Dumoulin, Antoine Triller, Jean-Louis Bessereau, Laure Rondi-Reig, Philippe Isope, and Fekrije Selimi
Subjects: synapse, plasticity, cerebellum, proteostasis, Medicine, Science, Biology (General), QH301-705.5
Abstract: Fine control of protein stoichiometry at synapses underlies brain function and plasticity. How proteostasis is controlled independently for each type of synaptic protein in a synapse-specific and activity-dependent manner remains unclear. Here, we show that Susd4, a gene coding for a complement-related transmembrane protein, is expressed by many neuronal populations starting at the time of synapse formation. Constitutive loss-of-function of Susd4 in the mouse impairs motor coordination adaptation and learning, prevents long-term depression at cerebellar synapses, and leads to misregulation of activity-dependent AMPA receptor subunit GluA2 degradation. We identified several proteins with known roles in the regulation of AMPA receptor turnover, in particular ubiquitin ligases of the NEDD4 subfamily, as SUSD4 binding partners. Our findings shed light on the potential role of SUSD4 mutations in neurodevelopmental diseases.
Published: 2021
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5. Anatomical and physiological foundations of cerebello-hippocampal interaction

Author: Thomas Charles Watson, Pauline Obiang, Arturo Torres-Herraez, Aurélie Watilliaux, Patrice Coulon, Christelle Rochefort, and Laure Rondi-Reig
Subjects: cerebellum, hippocampus, anatomy, physiology, spatial navigation, Medicine, Science, Biology (General), QH301-705.5
Abstract: Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde transneuronal tracer in mice, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally suggest that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6–12 Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.
Published: 2019
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6. Complementary Roles of the Hippocampus and the Dorsomedial Striatum during Spatial and Sequence-Based Navigation Behavior.

Author: Céline Fouquet, Bénédicte M Babayan, Aurélie Watilliaux, Bruno Bontempi, Christine Tobin, and Laure Rondi-Reig
Subjects: Medicine, Science
Abstract: We investigated the neural bases of navigation based on spatial or sequential egocentric representation during the completion of the starmaze, a complex goal-directed navigation task. In this maze, mice had to swim along a path composed of three choice points to find a hidden platform. As reported previously, this task can be solved by using two hippocampal-dependent strategies encoded in parallel i) the allocentric strategy requiring encoding of the contextual information, and ii) the sequential egocentric strategy requiring temporal encoding of a sequence of successive body movements associated to specific choice points. Mice were trained during one day and tested the following day in a single probe trial to reveal which of the two strategies was spontaneously preferred by each animal. Imaging of the activity-dependent gene c-fos revealed that both strategies are supported by an overlapping network involving the dorsal hippocampus, the dorsomedial striatum (DMS) and the medial prefrontal cortex. A significant higher activation of the ventral CA1 subregion was observed when mice used the sequential egocentric strategy. To investigate the potential different roles of the dorsal hippocampus and the DMS in both types of navigation, we performed region-specific excitotoxic lesions of each of these two structures. Dorsal hippocampus lesioned mice were unable to optimally learn the sequence but improved their performances by developing a serial strategy instead. DMS lesioned mice were severely impaired, failing to learn the task. Our data support the view that the hippocampus organizes information into a spatio-temporal representation, which can then be used by the DMS to perform goal-directed navigation.
Published: 2013
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7. A Liaison Brought to Light: Cerebellum-Hippocampus, Partners for Spatial Cognition

Author: Laure Rondi-Reig, Anne-Lise Paradis, Mehdi Fallahnezhad, Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), The National Agency for Research ANR-17-CE16-0019-03 (SynPredict), and ANR-18-CE16-0010-02 (RewInhib) supported LRR and MF. ANR-17-CE37-0015-02 (Navi-GPS) and SATT Lutech supported LRR and ALP., ANR-17-CE37-0015,NaviGPS,la Navigation au delà de l'hippocampe: Comment coder ses déplacements propres en tenant compte de l'environnement ?(2017), ANR-18-CE16-0010,RewInhib,Etude du circuit cérébelleux inhibiteur lors d'une tâche orienté vers la récompense(2018), ANR-17-CE16-0019,SynPredict,Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux(2017), Paradis, Anne-Lise, la Navigation au delà de l'hippocampe: Comment coder ses déplacements propres en tenant compte de l'environnement ? - - NaviGPS2017 - ANR-17-CE37-0015 - AAPG2017 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Etude du circuit cérébelleux inhibiteur lors d'une tâche orienté vers la récompense - - RewInhib2018 - ANR-18-CE16-0010 - AAPG2018 - VALID, and Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux - - SynPredict2017 - ANR-17-CE16-0019 - AAPG2017 - VALID
Subjects: Neurons, Hippocampus Introduction: Cerebellum and Spatial Cognition, Cognition, Multimodal sensory information, Neurology, Cerebellum, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Neurology (clinical), Hippocampus, Navigation, Spatial cognition, Spatial Navigation
Abstract: International audience; This review focuses on the functional and anatomical links between the cerebellum and the hippocampus and the role of their interplay in goal-directed navigation and spatial cognition. We will describe the interactions between the cerebellum and the hippocampus at different scales: a macroscopic scale revealing the joint activations of these two structures at the level of neuronal circuits, a mesoscopic scale highlighting the synchronization of neuronal oscillations, and finally a cellular scale where we will describe the activity of hippocampal neuronal assemblies following a targeted manipulation of the cerebellar system. We will take advantage of this framework to summarize the different anatomical pathways that may sustain this multiscale interaction. We will finally consider the possible influence of the cerebellum on pathologies traditionally associated with hippocampal dysfunction.
Published: 2022

8. Preserved Navigation abilities and Spatio-Temporal Memory in individuals with Autism Spectrum Disorder

Author: Charles Laidi, Nathan Neu, Aurélie Watilliaux, Axelle Martinez‐Teruel, Mihoby Razafinimanana, Jennifer Boisgontier, Sevan Hotier, Marc‐Antoine d'Albis, Richard Delorme, Anouck Amestoy, Štefan Holiga, Myriam Ly‐Le Moal, Pierrick Coupé, Marion Leboyer, Josselin Houenou, Laure Rondi‐Reig, Anne‐Lise Paradis, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cerebellum Navigation and Memory Team [IBPS] (CeZaMe), Neurosciences Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré, Institut Roche [Boulogne-Billancourt, France], Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Investissements d'Avenir programs managed by the ANR under references ANR-11-IDEX-004-02 (Labex BioPsy) and ANR-10-COHO-10-01 and CNRS, and via collaboration with the Roche Institute for Research and Translational Medicine., CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Neuroscience Paris Seine (NPS), Fondation FondaMental [Créteil], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Charles PERRENS, Patch-based processing for medical and natural images (PICTURA), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Autism Spectrum Disorder, Memory, General Neuroscience, Cerebellum, [SCCO.NEUR]Cognitive science/Neuroscience, Adults, Neurology (clinical), Genetics (clinical), Spatial Navigation
Abstract: International audience; Cerebellar abnormalities have been reported in autism spectrum disorder (ASD). Beyond its role in hallmark features of ASD, the cerebellum and its connectivity with forebrain structures also play a role in navigation. However, the current understanding of navigation abilities in ASD is equivocal, as is the impact of the disorder on the functional anatomy of the cerebellum. In the present study, we investigated the navigation behavior of a population of ASD and typically developing (TD) adults related to their brain anatomy as assessed by structural and functional MRI at rest. We used the Starmaze task, which permits assessing and distinguishing two complex navigation behaviors, one based on allocentric and the other on egocentric learning of a route with multiple decision points. Compared to TD controls, individuals with ASD showed similar exploration, learning, and strategy performance and preference. In addition, there was no difference in the structural or functional anatomy of the cerebellar circuits involved in navigation between the two groups. The findings of our work suggest that navigation abilities, spatio-temporal memory, and their underlying circuits are preserved in individuals with ASD.
Published: 2022

9. Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum ofShank3mutant mice

Author: Allain-Thibeault, Ferhat, primary, Elisabeth, Verpy, additional, Anne, Biton, additional, Benoît, Forget, additional, de Chaumont, Fabrice, additional, Florian, Mueller, additional, Anne-Marie, Le Sourd, additional, Sabrina, Coqueran, additional, Julien, Schmitt, additional, Christelle, Rochefort, additional, Laure, Rondi-Reig, additional, Aziliz, Leboucher, additional, Anne, Boland, additional, Bertrand, Fin, additional, François, Deleuze Jean, additional, Boeckers, Tobias M., additional, Elodie, Ey, additional, and Thomas, Bourgeron, additional
Published: 2022
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10. Chapitre 3. Étude des systèmes de mémoire dans le cadre d’un comportement : la navigation

Author: Laure Rondi-Reig
Published: 2021

11. Cerebellar Control of a Unitary Head Direction Sense

Author: Julia Le Méro, Xhensjana Zenelaj, Christelle Rochefort, Laure Rondi-Reig, Jean Vincent, Mehdi Fallahnezhad, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Cerebellum Navigation and Memory Team (CeZaMe), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Rondi-Reig, Laure, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS)
Subjects: Cerebellum, Head (linguistics), Sensory system, Head direction cell, Biology, Unitary state, 03 medical and health sciences, 0302 clinical medicine, medicine, Premovement neuronal activity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Control (linguistics), Angular head velocity, Attractor network, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Representation (systemics), Retrosplenial cortex, Continuous attractor network, medicine.anatomical_structure, Anterodorsal thalamus, Speed cell, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery
Abstract: The head-direction (HD) system, a key neural circuit for navigation, consists of several anatomical structures containing neurons selective to the animal’s head direction. HD cells exhibit ubiquitous temporal coordination across brain regions, independently of the animal’s behavioral state or sensory inputs. Such temporal coordination mediates a single, stable, and persistent HD signal, which is essential for intact orientation. However, the mechanistic processes behind the temporal organization of HD cells are unknown. By manipulating the cerebellum, we identify pairs of HD cells recorded from two brain structures (anterodorsal thalamus and retrosplenial cortex) that lose their temporal coordination, specifically during the removal of the external sensory inputs. Further, we identify distinct cerebellar mechanisms that participate in the spatial stability of the HD signal depending on sensory signals. We show that while cerebellar protein phosphatase 2B-dependent mechanisms facilitate the anchoring of the HD signal on the external cues, the cerebellar protein kinase C-dependent mechanisms are required for the stability of the HD signal by self-motion cues. These results indicate that the cerebellum contributes to the preservation of a single and stable sense of direction.
Published: 2021

12. Cerebellum and spatial cognition: A connectionist approach.

Author: Jean-Baptiste Passot, Laure Rondi-Reig, and Angelo Arleo
Published: 2009

13. Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

Author: Keerthana Iyer, Fernando A Giuliani, Laure Rondi-Reig, Philippe Isope, Yann Nadjar, Antoine Triller, Jean-Louis Bessereau, Mélanie Albert, Andréa Dumoulin, Séverine M. Sigoillot, Oana Vigy, Maxime Veleanu, Jean Vincent, Mélanie Carquin, Anouar Khayachi, Célia Bosso-Lefèvre, Martial Séveno, Fekrije Selimi, Inés González-Calvo, Sylvana Tahraoui, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, Hal Sorbonne Université, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Sushi domain, cerebellum, QH301-705.5, Science, [SDV]Life Sciences [q-bio], Protein subunit, AMPA receptor, Motor Activity, General Biochemistry, Genetics and Molecular Biology, neuroscience, Synapse, Mice, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, synapse, Animals, Learning, Biology (General), mouse, Complement Inactivator Proteins, Neuronal Plasticity, proteostasis, General Immunology and Microbiology, biology, General Neuroscience, Membrane Proteins, General Medicine, Transmembrane protein, [SDV] Life Sciences [q-bio], 030104 developmental biology, Proteostasis, plasticity, Synaptic plasticity, biology.protein, Medicine, Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract: Fine control of protein stoichiometry at synapses underlies brain function and plasticity. How proteostasis is controlled independently for each type of synaptic protein in a synapse-specific and activity-dependent manner remains unclear. Here, we show that Susd4, a gene coding for a complement-related transmembrane protein, is expressed by many neuronal populations starting at the time of synapse formation. Constitutive loss-of-function of Susd4 in the mouse impairs motor coordination adaptation and learning, prevents long-term depression at cerebellar synapses, and leads to misregulation of activity-dependent AMPA receptor subunit GluA2 degradation. We identified several proteins with known roles in the regulation of AMPA receptor turnover, in particular ubiquitin ligases of the NEDD4 subfamily, as SUSD4 binding partners. Our findings shed light on the potential role of SUSD4 mutations in neurodevelopmental diseases.
Published: 2021

14. Author response: Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

Author: Célia Bosso-Lefèvre, Oana Vigy, Jean Vincent, Fernando A Giuliani, Jean-Louis Bessereau, Mélanie Carquin, Maxime Veleanu, Antoine Triller, Anouar Khayachi, Inés González-Calvo, Sylvana Tahraoui, Keerthana Iyer, Laure Rondi-Reig, Philippe Isope, Andréa Dumoulin, Yann Nadjar, Mélanie Albert, Séverine M. Sigoillot, Martial Séveno, and Fekrije Selimi
Subjects: Sushi domain, Synaptic plasticity, Biology, Motor learning, Neuroscience
Published: 2021

15. Flexibility as a marker of early cognitive decline in humanized apolipoprotein E ε4 (ApoE4) mice

Author: Mathieu Boucher, Laure Rondi-Reig, Julien Schmitt, Anne-Lise Paradis, Laurent Andrieu, and Pascal Barnéoud
Subjects: 0301 basic medicine, Apolipoprotein E, Male, medicine.medical_specialty, Aging, Adult male, Apolipoprotein E4, Spatial Learning, Mice, Transgenic, Normal aging, 03 medical and health sciences, 0302 clinical medicine, Memory, Internal medicine, mental disorders, medicine, Animals, Cognitive Dysfunction, Young adult, Cognitive decline, business.industry, General Neuroscience, Flexibility (personality), Cognition, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, Spatial learning, lipids (amino acids, peptides, and proteins), Neurology (clinical), Geriatrics and Gerontology, business, human activities, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology, Spatial Navigation
Abstract: To test the hypothesis that ApoE4 may be involved in cognitive deficits associated with aging, we investigated the impact of APOE4 status and aging on the flexibility and memory components of spatial learning in mice. Young adult (6 months) and middle-aged (14 months) ApoE4, ApoE3 and C57BL/6 adult male mice were tested for flexibility in an aquatic Y-maze, and for spatio-temporal memory acquisition in the Starmaze. Our results revealed a flexibility deficit of the 6-month-old ApoE4 mice compared to controls. However, this deficit was not associated with spatio-temporal memory deficit at the same age. Importantly, the ApoE4 flexibility deficit did not increase with age, nor turn into memory deficit, or was able to predict individual variations of memory performance at 14 months. By contrast, control ApoE3 mice showed a decline of flexibility at 14 months resulting in performance similar to that of ApoE4. Overall, our results suggest that ApoE4 could be associated with an acceleration of the flexibility decrease otherwise observed in normal aging.
Published: 2020

16. Author Correction: A hippocampo-cerebellar centred network for the learning and execution of sequence-based navigation

Author: Laure Rondi-Reig, Anne-Lise Paradis, Benedicte M. Babayan, Aurélie Watilliaux, Benoît Girard, Guillaume Viejo, Sorbonne Université (SU), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Architectures et modèles d'Adptation et de la cognition (AMAC), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Computer science, Speech recognition, [SDV]Life Sciences [q-bio], Models, Neurological, lcsh:Medicine, Hippocampus, Basal Ganglia, 03 medical and health sciences, Mice, 0302 clinical medicine, Memory, Cerebellum, Orientation, Neural Pathways, Animals, Learning, Computer Simulation, lcsh:Science, Author Correction, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Sequence (medicine), Cerebral Cortex, 0303 health sciences, Multidisciplinary, lcsh:R, Mice, Inbred C57BL, Space Perception, lcsh:Q, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030217 neurology & neurosurgery
Abstract: How do we translate self-motion into goal-directed actions? Here we investigate the cognitive architecture underlying self-motion processing during exploration and goal-directed behaviour. The task, performed in an environment with limited and ambiguous external landmarks, constrained mice to use self-motion based information for sequence-based navigation. The post-behavioural analysis combined brain network characterization based on c-Fos imaging and graph theory analysis as well as computational modelling of the learning process. The study revealed a widespread network centred around the cerebral cortex and basal ganglia during the exploration phase, while a network dominated by hippocampal and cerebellar activity appeared to sustain sequence-based navigation. The learning process could be modelled by an algorithm combining memory of past actions and model-free reinforcement learning, which parameters pointed toward a central role of hippocampal and cerebellar structures for learning to translate self-motion into a sequence of goal-directed actions.
Published: 2019

17. Validation of memory assessment in the Starmaze task: Data from 14 month-old APPPS1 mice and controls

Author: Anne-Lise Paradis, Mathieu Boucher, Julien Schmitt, Laure Rondi-Reig, Pascal Barneoud, Laurent Andrieu, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurodegeneration Cluster, Rare & Neurologic Diseases Research, Sanofi Aventis R&D [Chilly-Mazarin], IT&M STATS, Groupe IT&M, Biostatistics & Programming Department, Non-Clinical Efficacy & Safety team, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Paradis, Anne-Lise, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Aging, medicine.medical_specialty, Science (General), Computer applications to medicine. Medical informatics, R858-859.7, Navigation behavior, Normal aging, Audiology, Task (project management), Sequence memory, Q1-390, 03 medical and health sciences, 0302 clinical medicine, medicine, Spatio-temporal memory, Cognitive decline, Alzheimer’s Disease (AD), Data Article, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Familial form, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, robustness assessment, Flexibility (personality), medicine.disease, transgenic mouse model, 030220 oncology & carcinogenesis, Alzheimer's disease (AD), Spatial learning, APPPS1, Alzheimer's disease, Psychology, sequence memory
Abstract: International audience; This article describes navigation data of 14 month-old APPPS1 and C57Bl6 in the Starmaze task. These data were acquired as positive controls of memory deficit in a model of the familial form of Alzheimers’s disease (see Schmitt et al., Flexibility as a marker of early cognitive decline in humanized Apolipoprotein E ε4 (ApoE4) mice, Neurobiol Aging, 2021). They were acquired in a reduced version of the Starmaze environment and accompanied by a number of acquisitions in different control groups at 6 and 14 months to assess the robustness of the procedure and its associated memory scores. These data illustrate the extraction of a variety of navigation scores (including search strategy, spatial learning and memory) and provide a reference of navigation data in the Starmaze task for healthy 6-month-old controls, normal aging and a model of pathological memory deficit.
Published: 2021

18. Choroid plexus APP regulates adult brain proliferation and animal behavior

Author: Vanessa Oliveira Moreira, Jean Vincent, Laure Rondi-Reig, Ulrike Müller, Alain Prochiantz, Chantal Le Poupon, Glenn Dallérac, Max Richter, Karen Arnaud, and Ariel A. Di Nardo
Subjects: 0303 health sciences, biology, Dentate gyrus, Subventricular zone, Hippocampus, Long-term potentiation, Hippocampal formation, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, medicine.anatomical_structure, Amyloid precursor protein, biology.protein, medicine, Choroid plexus, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Elevated amyloid precursor protein (APP) expression in the choroid plexus suggests an important role for extracellular APP metabolites in cerebrospinal fluid. Despite widespread App brain expression, we hypothesized that specifically targeting choroid plexus expression could alter animal physiology. Through various genetic and viral approaches in the adult mouse, we show that choroid plexus APP levels significantly impacted proliferation in both subventricular zone and hippocampus dentate gyrus neurogenic niches. Given the role of Aβ peptides in Alzheimer disease pathogenesis, we also tested whether favoring the production of Aβ in choroid plexus could negatively affect niche functions. After AAV5-mediated long-term expression of human mutated APP specifically in the choroid plexus of adult wild type mice, we observe reduced niche proliferation, behavioral defects in reversal learning, and deficits in hippocampal long-term potentiation. Our findings highlight the unique role played by the choroid plexus in regulating brain function, and suggest that targeting APP in choroid plexus may provide a means to improve hippocampus function and alleviate disease-related burdens.
Published: 2019

19. Anatomical and physiological foundations of cerebello-hippocampal interaction

Author: Patrice Coulon, Arturo Torres-Herraez, Christelle Rochefort, Pauline Obiang, Laure Rondi-Reig, Thomas C. Watson, Aurélie Watilliaux, Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), ANR-17-CE16-0019,SynPredict,Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux(2017), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Male, Cerebellum, anatomy, cerebellum, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Rabies, hippocampus, QH301-705.5, Science, Hippocampus, spatial navigation, Local field potential, Hippocampal formation, Biology, Spatial memory, General Biochemistry, Genetics and Molecular Biology, neuroscience, 03 medical and health sciences, 0302 clinical medicine, Neural Pathways, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Premovement neuronal activity, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology (General), mouse, Neurons, General Immunology and Microbiology, General Neuroscience, Motor control, General Medicine, Electric Stimulation, Mice, Inbred C57BL, Brain region, 030104 developmental biology, medicine.anatomical_structure, nervous system, Rabies virus, physiology, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nerve Net, Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract: International audience; Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde transneuronal tracer in mice, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally suggest that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6-12 Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.
Published: 2019

20. Impaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation

Author: Christelle Rochefort, Chris I. De Zeeuw, Lucille Tallot, Julie M. Lefort, Jean Vincent, Frédéric Jarlier, Laure Rondi-Reig, Sorbonne Université (SU), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Neurosciences, Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Computer science, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Cerebellar Purkinje cell, 02 engineering and technology, Hippocampal formation, Hippocampus, Spatial memory, Article, General Biochemistry, Genetics and Molecular Biology, Mice, Purkinje Cells, 03 medical and health sciences, Orientation (mental), Cerebellum, Animals, lcsh:Science, Orientation, Spatial, Mice, Knockout, Neuronal Plasticity, Multidisciplinary, Calcineurin, Representation (systemics), Long-term potentiation, General Chemistry, 021001 nanoscience & nanotechnology, Cellular neuroscience, Navigation, Familiar environment, Mice, Inbred C57BL, 030104 developmental biology, Space Perception, Models, Animal, lcsh:Q, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Spatial maps, Cues, 0210 nano-technology, Neuroscience, Spatial Navigation
Abstract: Cerebellar activity supported by PKC-dependent long-term depression in Purkinje cells (PCs) is involved in the stabilization of self-motion based hippocampal representation, but the existence of cerebellar processes underlying integration of allocentric cues remains unclear. Using mutant-mice lacking PP2B in PCs (L7-PP2B mice) we here assess the role of PP2B-dependent PC potentiation in hippocampal representation and spatial navigation. L7-PP2B mice display higher susceptibility to spatial map instability relative to the allocentric cue and impaired allocentric as well as self-motion goal-directed navigation. These results indicate that PP2B-dependent potentiation in PCs contributes to maintain a stable hippocampal representation of a familiar environment in an allocentric reference frame as well as to support optimal trajectory toward a goal during navigation., It is known that Purkinje cell PKC-dependent depression is involved in the stabilization of self-motion based hippocampal representation. Here the authors describe decreased stability of hippocampal place cells based on allocentric cues in mice lacking Purkinje cell PP2B-dependent potentiation.
Published: 2019

21. Author response: Anatomical and physiological foundations of cerebello-hippocampal interaction

Author: Thomas C. Watson, Patrice Coulon, Arturo Torres-Herraez, Aurélie Watilliaux, Christelle Rochefort, Pauline Obiang, and Laure Rondi-Reig
Subjects: business.industry, Medicine, Hippocampal formation, business, Neuroscience
Published: 2019

22. SUSD4 Controls Activity-Dependent Degradation of AMPA Receptor GLUA2 and Synaptic Plasticity

Author: Philippe Isope, Oana Vigy, Célia Bosso-Lefèvre, Andréa Dumoulin, Mélanie Albert, Fernando A Giuliani, Jean-Louis Bessereau, Inés González-Calvo, Sylvana Tahraoui, Séverine M. Sigoillot, Anouar Khayachi, Maxime Veleanu, Mélanie Carquin, Keerthana Iyer, Yann Nadjar, Martial Séveno, Laure Rondi-Reig, Antoine Triller, Fekrije Selimi, and Jean Vincent
Subjects: 0303 health sciences, biology, Protein subunit, NEDD4, AMPA receptor, Transmembrane protein, Motor coordination, 03 medical and health sciences, 0302 clinical medicine, Proteostasis, Ubiquitin, Synaptic plasticity, biology.protein, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: SummaryAt excitatory synapses, the choice between recycling or degradation of glutamate AMPA receptors controls the direction of synaptic plasticity. In this context, how the degradation machinery is targeted to specific synaptic substrates in an activity-dependent manner is not understood. Here we show that SUSD4, a complement-related transmembrane protein, is a tether for HECT ubiquitin ligases of the NEDD4 subfamily, which promote the degradation of a large number of cellular substrates. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function ofSusd4in the mouse prevents activity-dependent degradation of the GLUA2 AMPA receptor subunit and long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. SUSD4 could thus act as an adaptor targeting NEDD4 ubiquitin ligases to AMPA receptors during long-term synaptic plasticity. These findings shed light on the potential contribution ofSUSD4mutations to the etiology of neurodevelopmental diseases.
Published: 2019
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23. Anatomical and physiological foundations of cerebello-hippocampal interactions

Author: Christelle Rochefort, Pauline Obiang, Thomas C. Watson, Arturo Torres-Herraez, Laure Rondi-Reig, Aurélie Watilliaux, and Patrice Coulon
Subjects: Cerebellum, Brain region, medicine.anatomical_structure, nervous system, medicine, Premovement neuronal activity, Hippocampus, Motor control, Local field potential, Hippocampal formation, Biology, Neuroscience, Spatial memory
Abstract: Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such interactions remains unknown. Using rabies virus as retrograde transneuronal tracer, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally demonstrate that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6-12Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.
Published: 2018

24. P1‐092: NEUROPROTECTIVE EFFECTS OF PKR KNOCKOUT IN 5XFAD ALZHEIMER MICE AND NEURON‐MICROGLIA CO‐CULTURES

Author: Eliane F. Meurs, Julien Schmitt, Claire Paquet, Jean-Antoine Girault, François Mouton-Liger, Laure Rondi Reig, Albert Giralt, Sylvie Thomasseau, Marion Tible, and Jacques Hugon
Subjects: Microglia, Epidemiology, Health Policy, Biology, Protein kinase R, Neuroprotection, Psychiatry and Mental health, Cellular and Molecular Neuroscience, medicine.anatomical_structure, Developmental Neuroscience, medicine, Neurology (clinical), Neuron, Geriatrics and Gerontology, Neuroscience
Published: 2018

25. Le codage de l’espace

Author: Laure Rondi-Reig
Subjects: Cognitive science, Neural activity, business.industry, Coding (therapy), Medicine, General Medicine, Space (commercial competition), business, General Biochemistry, Genetics and Molecular Biology
Abstract: The Nobel Prize in Medecine or Physiology for 2014 has been awarded to three neuroscientists: John O'Keefe, May-Britt Moser and Edvard Moser for "their discoveries of cells that constitute a positioning system in the brain". This rewards innovative ideas which led to the development of intracerebral recording techniques in freely moving animals, thus providing links between behavior and physiology. This prize highlights how neural activity sustains our ability to localize ourselves and move around in the environment. This research provides key insights on how the brain drives behavior.
Published: 2015

26. Cerebellar Contribution to Spatial Navigation: New Insights into Potential Mechanisms

Author: Julie M. Lefort, Laure Rondi-Reig, Christelle Rochefort, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cerebellum, Plasticity, Place cell, Hippocampus, Hippocampal formation, Spatial memory, Task (project management), 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, 030304 developmental biology, Cued speech, 0303 health sciences, Navigation, Electrophysiology, medicine.anatomical_structure, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Psychology, Neuroscience, 030217 neurology & neurosurgery, Spatial Navigation, L7-PKCI
Abstract: SIXTH INTERNATIONAL SYMPOSIUM OF SRC, Rome, ITALY, JUL 03-04, 2014; International audience; The contribution of the cerebellum to the non-motor aspects of spatial navigation is now established, but the mechanisms of its participation remain unclear. The L7-PKCI mouse model, in which inhibited PKC activity suppresses parallel fiber-Purkinje cell long-term depression (LTD), provides the opportunity to study their spatial abilities in the absence of any motor impairment. L7-PKCI mice are deficient in the spatial but not the cued version of the watermaze task. Their performances are preserved when alleys guide their trajectories in the starmaze task, suggesting that cerebellar PKC-dependent mechanisms are required for the production of an optimal trajectory toward a goal. Furthermore, electrophysiological recordings in freely moving L7-PKCI mice revealed that their hippocampal place cell properties are affected when they have to rely on self motion information: in the absence of external information as well as in a conflicting situation between self-motion and external information. This suggests that the cerebellum is involved in the processing of self-motion information and is required for the construction of the spatial representation in the hippocampus.
Published: 2015

27. [P1–115]: THE KINASE PKR INTERFERES WITH BRAIN AMYLOID ACCUMULATION IN 5XFAD MICE

Author: Marion Tible, Karim Farid, François Mouton-Liger, Jacques Hugon, Claire Paquet, Sarah Gourmaud, Laure Rondi Reig, Jean-Antoine Girault, Julien Schmitt, and Eliane F. Meurs
Subjects: Amyloid, Epidemiology, Kinase, business.industry, Health Policy, Protein kinase R, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published: 2017

28. Cerebellar volume in autism: Meta-analysis and analysis of the ABIDE cohort

Author: Richard Delorme, Nicolas Traut, Anne-Lise Paradis, Roberto Toro, Laure Rondi-Reig, Anita Beggiato, Thomas Bourgeron, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Autism brain imaging data exchange, business.industry, Publication bias, medicine.disease, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Autism spectrum disorder, Endophenotype, Meta-analysis, Cohort, medicine, Autism, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 10. No inequality, Association (psychology), business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Cerebellar volume abnormalities have been often suggested as a possible endophenotype for autism spectrum disorder (ASD). We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature, and an analysis of the Autism Brain Imaging Data Exchange (ABIDE) cohort. Our meta-analysis sought to determine a combined effect size of ASD diagnosis on different measures of the cerebellar anatomy, as well as the effect of possible factors of variability across studies. We then analysed the cerebellar volume of 328 patients and 353 controls from the ABIDE project. The meta-analysis of the literature suggested a weak but significant association between ASD diagnosis and increased cerebellar volume (p=0.049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies in the literature were generally underpowered, however, the number of statistically significant findings was larger than expected. Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex and IQ were important sources of cerebellar volume variability, however, independent of autism diagnosis.
Published: 2017
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29. Oscillatory Dynamics and Place Field Maps Reflect Hippocampal Ensemble Processing of Sequence and Place Memory under NMDA Receptor Control

Author: Cyriel M. A. Pennartz, Martin Vinck, Henrique Cabral, Celine Fouquet, Laure Rondi-Reig, Francesco P. Battaglia, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), STW [AET7613], EU [270108], European Commission [ENLIGHTENMENT 284801], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cognitive and Systems Neuroscience (SILS, FNWI), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Neuroinformatics, Patch-Clamp Techniques, Neuroscience(all), Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Action Potentials, Hippocampus, Nerve Tissue Proteins, Sensory system, Serial Learning, Hippocampal formation, Receptors, N-Methyl-D-Aspartate, Mice, 03 medical and health sciences, 0302 clinical medicine, Biological Clocks, Memory, Animals, Maze Learning, Control (linguistics), 030304 developmental biology, Sequence (medicine), Mice, Knockout, Neurons, Analysis of Variance, 0303 health sciences, Spectrum Analysis, General Neuroscience, Dynamics (mechanics), Brain Waves, Nonlinear Dynamics, nervous system, Space Perception, Forebrain, NMDA receptor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Carrier Proteins, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Place coding in the hippocampus requires flexible combination of sensory inputs (e.g., environmental and self-motion information) with memory of past events. We show that mouse CA1 hippocampal spatial representations may either be anchored to external landmarks (place memory) or reflect memorized sequences of cell assemblies depending on the behavioral strategy spontaneously selected. These computational modalities correspond to different CA1 dynamical states, as expressed by theta and low- and high-frequency gamma oscillations, when switching from place to sequence memory-based processing. These changes are consistent with a shift from entorhinal to CA3 input dominance on CA1. In mice with a deletion of forebrain NMDA receptors, the ability of place cells to maintain a map based on sequence memory is selectively impaired and oscillatory dynamics are correspondingly altered, suggesting that oscillations contribute to selecting behaviorally appropriate computations in the hippocampus and that NMDA receptors are crucial for this function.
Published: 2014

30. Inhibition de PKR dans la maladie d’Alzheimer : un rôle anti-inflammatoire, anti-apoptotique et anti-amyloïde

Author: Sylvie Thomasseau, Laure Rondi Reig, Marion Tible, Jacques Hugon, Jean-Antoine Girault, Eliane F. Meurs, Claire Paquet, and François Mouton-Liger
Subjects: Anatomy
Abstract: But de l’etude La maladie d’Alzheimer (MA) se caracterise neuropathologiquement par l’agregation de peptides amyloides et une hyperphosphorylation de Tau, associees a une mort neuronale accrue et une inflammation locale. Dans ce contexte, nous nous sommes interesses a PKR (dsRNA-binding protein kinase), une proteine pro-apoptotique activee par phosphorylation. Notre equipe a d’ores et deja demontre que la presence de pPKR dans le liquide cephalo-rachidien (LCR) etait predictif du declin cognitif des patients atteints de MA et etait un marqueur present au stade prodromal. Nous avons donc cherche a comprendre son role dans la mise en place de l’inflammation, de la mort neuronale et dans la regulation de la charge amyloide. Methodes En utilisant des souris transgeniques 5xFAD, un modele murin classique de la MA depourvu de taupathies, des souris PKR KO et des souris issues de leur croisement (5xFADxPKR KO), nous avons etudie par des techniques proteomiques (western blot, Elisa, Luminex) et immunohistochimiques (IHC, IF) les marqueurs de la mort neuronale (caspase-3, pBLC2, Bax, fluorojade) de l’inflammation (cytokines, IBA1) et de la charge amyloide (BACE-1, Aβ, APP, MOAB). Dans des co-cultures primaires de neurones et microglies PKR KO ou non, traites ou non au LPS (induction d’un stress), nous avons realise des analyses de la reponse inflammatoire par western blot et Luminex (cytokines) et de la mort cellulaire (TUNEL). Resultats La deletion de PKR chez les souris 5xFAD entraine une baisse significative de l’inflammation, de la mort neuronale et de la charge amyloide. La deletion de PKR dans les microglies en culture entraine une baisse de la reponse inflammatoire au stress ainsi qu’une baisse de la mort cellulaire. Conclusion Ces resultats indiquent PKR comme une cible therapeutique et diagnostique future.
Published: 2017

31. Mature Purkinje Cells Require the Retinoic Acid-Related Orphan Receptor-α (RORα) to Maintain Climbing Fiber Mono-Innervation and Other Adult Characteristics

Author: Xiao Ru Chen, Vidjeacoumary Cannaya, Rachel M. Sherrard, Laure Rondi-Reig, Rosine Wehrlé, Ann M. Lohof, Hasan X. Avci, Mohamed Doulazmi, Isabelle Dusart, Jean Mariani, Constantino Sotelo, Guilan Vodjdani, Nicolas Heck, Christelle Rochefort, Marie-Pierre Morel, Serge Marty, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CNRS, UPMC, Spanish Ministry of Science and Innovation [BFU2010-27326], [ANR-07-NEURO-043-01], Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Ministerio de Ciencia e Innovación (España), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Somatic cell, Purkinje cell, Retinoic acid, Cell Count, Polymerase Chain Reaction, Mice, Purkinje Cells, chemistry.chemical_compound, Nerve Fibers, 0302 clinical medicine, Postural Balance, Mice, Knockout, Orphan receptor, 0303 health sciences, Behavior, Animal, General Neuroscience, Cell Differentiation, Forkhead Transcription Factors, Nuclear Receptor Subfamily 1, Group F, Member 1, Articles, Climbing fiber, Immunohistochemistry, Cell biology, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Genetic Vectors, Dendrite, Biology, 03 medical and health sciences, medicine, Animals, Humans, Interpersonal Relations, Muscle Strength, Transcription factor, 030304 developmental biology, Lentivirus, DNA, Axons, Mice, Inbred C57BL, Repressor Proteins, Microscopy, Electron, chemistry, Mutation, Vesicular Glutamate Transport Protein 1, Vesicular Glutamate Transport Protein 2, Soma, Neuroscience, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract: Neuronal maturation during development is a multistep process regulated by transcription factors. The transcription factor RORα (retinoic acid-related orphan receptor α) is necessary for early Purkinje cell (PC) maturation but is also expressed throughout adulthood. To identify the role of RORα in mature PCs, we used Cre-lox mouse genetic tools in vivo that delete it specifically from PCs between postnatal days 10-21. Up to 14 d of age, differences between mutant and control PCs were not detectable: both were mono-innervated by climbing fibers (CFs) extending along their well-developed dendrites with spiny branchlets. By week 4, mutant mice were ataxic, some PCs had died, and remaining PC soma and dendrites were atrophic, with almost complete disappearance of spiny branchlets. The innervation pattern of surviving RORα-deleted PCs was abnormal with several immature characteristics. Notably, multiple functional CF innervation was reestablished on these mature PCs, simultaneously with the relocation of CF contacts to the PC soma and their stem dendrite. This morphological modification of CF contacts could be induced even later, using lentivirus-mediated depletion of rora from adult PCs. These data show that the late postnatal expression of RORα cell-autonomously regulates the maintenance of PC dendritic complexity, and the CF innervation status of the PC (dendritic vs somatic contacts, and mono-innervation vs multi-innervation). Thus, the differentiation state of adult neurons is under the control of transcription factors; and in their absence, adult neurons lose their mature characteristics and acquire some characteristics of an earlier developmental stage., This work was supported by the CNRS, UPMC, and ANR-07-NEURO-043–01. C.S. was supported in part by the Spanish Ministry of Science and Innovation Grant BFU2010–27326.
Published: 2013

32. Pregnenolone sulfate and its enantiomer: Differential modulation of memory in a spatial discrimination task using forebrain NMDA receptor deficient mice

Author: Géraldine H. Petit, Yves Moricard, Laure Rondi-Reig, Douglas F. Covey, Christine Tobin, Yvette Akwa, and Kathiresan Krishnan
Subjects: Male, N-Methylaspartate, Hippocampus, Hippocampal formation, Receptors, N-Methyl-D-Aspartate, Article, Mice, chemistry.chemical_compound, Prosencephalon, Memory, otorhinolaryngologic diseases, medicine, Animals, Pharmacology (medical), Receptor, Biological Psychiatry, Mice, Knockout, Pharmacology, Chemistry, Stereoisomerism, Psychiatry and Mental health, nervous system, Neurology, Pregnenolone, Space Perception, Forebrain, NMDA receptor, Steroids, Neurology (clinical), Enantiomer, Pregnenolone sulfate, Neuroscience, medicine.drug
Abstract: This study examined the role of forebrain N-methyl-D-aspartate receptors (NMDA-Rs) in the promnesiant effects of natural (+) pregnenolone sulfate (PREGS) and its synthetic (−) enantiomer ent-PREGS in young adult mice. Using the two-trial arm discrimination task in a Y-maze, PREGS and ent-PREGS administration to control mice increased memory performances. In mice with a knock-out of the NR1 subunit of NMDA-Rs in the forebrain, the promnesiant effect of ent-PREGS was maintained whereas the activity of PREGS was lost. Memory enhancement by PREGS involves the NMDA-R activity in the hippocampal CA1 area and possibly in some locations of the cortical layers, whereas ent-PREGS acts independently of NMDA-R function.
Published: 2011

33. A new approach for modeling episodic memory from rodents to humans: The temporal order memory

Author: Laure Rondi-Reig, Christine Tobin, and Celine Fouquet
Subjects: Adaptive memory, Time Factors, Flexibility (personality), Hippocampus, Cognition, Models, Psychological, medicine.disease, Spatial memory, Behavioral Neuroscience, Mental Recall, Models, Animal, medicine, Animals, Humans, Semantic memory, Alzheimer's disease, Maze Learning, Psychology, Episodic memory, Neuroscience
Abstract: One of the crucial issues in actual research on memory disorders and particularly in Alzheimer's disease is the development of behavioral tasks accurately testing episodic memory, a type of memory sensitive to aging and altered early during neurodegenerative disorders. Translational research allowing comparison of similar memory properties between human and rodent models is a requirement for the finding of behavioral and cognitive biomarkers as well as molecular deficits associated to the pathology. In this review, we propose that the ability to remember an ordered sequence of choices during spatial navigation could be one of the episodic memory properties shared by human and rodent models. The ability to learn the correct sequence of choices depends on the hippocampus, requires flexibility and is particularly sensitive to age-related decline in rodents as in humans. In an innovative approach, we took advantage of a well characterized rodent navigation task, the starmaze, to develop a new model of episodic allowing creating and objective experimental testing of a personal past experience without requiring verbal report which can be transferred to human.
Published: 2010

34. Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation

Author: Anne-Lise Paradis, Christian F. Doeller, Karim Benchenane, Kinga Igloi, Neil Burgess, Alain Berthoz, Laure Rondi-Reig, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), EU, Agence Nationale de la Recherche, Fondation pour la Recherche Medicale (France), Medical Research Council, Wellcome Trust (UK), European Research Council [ERC-StG RECONTEXT 261177], Netherlands Organisation for Scientific Research (NWO-Vidi) [452-12-009], Collège de France (CdF (institution)), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Cerebellum, Cognitive Neuroscience, Posterior parietal cortex, Hippocampus, Hippocampal formation, Sequence learning, Spatial memory, Functional Laterality, Virtual reality, User-Computer Interface, Young Adult, Functional connectivity, Cellular and Molecular Neuroscience, Neural Pathways, Image Processing, Computer-Assisted, medicine, Humans, Maze Learning, Prefrontal cortex, sequence learning, medicine.diagnostic_test, fMRI, functional connectivity, Parietal lobe, Articles, spatial memory, Magnetic Resonance Imaging, Oxygen, ddc:128.37, medicine.anatomical_structure, nervous system, virtual reality, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Functional magnetic resonance imaging, 120 Memory and Space, Neuroscience, Spatial Navigation
Abstract: International audience; To examine the cerebellar contribution to human spatial navigation we used functional magnetic resonance imaging and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects of navigation. They further suggest that Crus I belongs to 2 nonmotor loops, involved in different strategies: placebased navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex, and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task.
Published: 2015

35. p53 Inactivation leads to impaired motor synchronization in mice

Author: Jonathan B. Weitzman, Ann M. Lohof, Aline Campana, Jean Mariani, Laure Rondi-Reig, F. Picquet, Christine Tobin, and Maurice Falempin
Subjects: Functional role, 0303 health sciences, Cerebellum, General Neuroscience, Behavioural analysis, Central nervous system, Biology, Pifithrin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine.anatomical_structure, chemistry, P53 protein, Synchronization (computer science), medicine, Motor Deficit, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53-null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo-cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin-a, into the cerebellum of wild-type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization.
Published: 2003

36. Hippocampal CA3 NMDA Receptors Are Crucial for Memory Acquisition of One-Time Experience

Author: Kazu Nakazawa, Linus D. Sun, Michael C. Quirk, Matthew A. Wilson, Laure Rondi-Reig, and Susumu Tonegawa
Subjects: Neuroscience(all), Action Potentials, Morris water navigation task, Hippocampus, Hippocampal formation, Receptors, N-Methyl-D-Aspartate, Lesion, Mice, 03 medical and health sciences, 0302 clinical medicine, Interneurons, Memory, medicine, Animals, Maze Learning, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Pyramidal Cells, General Neuroscience, Intervention studies, Mice, Mutant Strains, Electrodes, Implanted, Mice, Inbred C57BL, Rapid acquisition, nervous system, Mental Recall, Exploratory Behavior, NMDA receptor, Memory acquisition, medicine.symptom, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Lesion and pharmacological intervention studies have suggested that in both human patients and animals the hippocampus plays a crucial role in the rapid acquisition and storage of information from a novel one-time experience. However, how the hippocampus plays this role is poorly known. Here, we show that mice with NMDA receptor (NR) deletion restricted to CA3 pyramidal cells in adulthood are impaired in rapidly acquiring the memory of novel hidden platform locations in a delayed matching-to-place version of the Morris water maze task but are normal when tested with previously experienced platform locations. CA1 place cells in the mutant animals had place field sizes that were significantly larger in novel environments, but normal in familiar environments relative to those of control mice. These results suggest that CA3 NRs play a crucial role in rapid hippocampal encoding of novel information for fast learning of one-time experience.
Published: 2003
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37. The role of climbing and parallel fibers inputs to cerebellar cortex in navigation

Author: Laure Rondi-Reig, Jean Caston, Jean Mariani, and Nathalie Le Marec
Subjects: Male, Brain Mapping, Cerebellum, Computer science, Rats, Inbred Strains, Rats, Task (project management), Lesion, Cerebellar Cortex, Behavioral Neuroscience, Nerve Fibers, medicine.anatomical_structure, Escape Reaction, Motor Skills, Orientation, Climbing, Cerebellar cortex, medicine, Animals, medicine.symptom, Maze Learning, Neuroscience, Psychomotor Performance
Abstract: DA-HAN rats with partial or total lesion of climbing (CF) and parallel fibers (PF) inputs of the cerebellum were tested in a water task. Two different protocols were used, requiring to find either a non-visible or a visible platform. These two protocols were, respectively, designed to evaluate visuo-motor guidance (visible platform) and navigation (non-visible platform). Both groups of lesioned rats presented a deficit in the non-visible platform task but not in the visible platform one. The protocol of navigation we used was a fixed start–fixed arrival procedure. Totally lesioned animals were unable to learn to orient their body toward the non-visible platform and adopted instead a circling behavior. Our results suggest a role of cerebellar inputs (climbing (CF) and PF) in navigation.
Published: 2002

38. Single-trial properties of place cells in control and ca1 nmda receptor subunit 1-ko mice

Author: Henrique Cabral, Francesco P. Battaglia, Cyriel M. A. Pennartz, Laure Rondi-Reig, Celine Fouquet, Cognitive and Systems Neuroscience (SILS, FNWI), Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), STW Grant [AET7613], EU FP7 Grant [270108], Future and Emerging Technologies program within the Seventh Framework Program [284801], Neurosciences Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Neuroinformatics, Place cell, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Action Potentials, Hippocampus, Context (language use), Motor Activity, Receptors, N-Methyl-D-Aspartate, Mice, Animals, place cells, CA1 Region, Hippocampal, Spatial analysis, Jitter, single-trial, Mice, Knockout, Physics, Communication, Neuronal Plasticity, business.industry, General Neuroscience, Articles, Field (geography), NMDA, Synaptic plasticity, NMDA receptor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Neuroscience
Abstract: International audience; The NMDA receptor plays a key role in synaptic plasticity and its disruption leads to impaired spatial representation in the CA1 area of the hippocampus, with place cells exhibiting larger place fields (McHugh et al., 1996). Place fields are defined by the spatial and nonspatial inputs of a given place and context, by intrinsic network processes, such as phase precession, but also by the matching of these inputs to a pre-existing spatial representation. Larger place fields maybe a consequence of spatially widened firing upon a single crossing of a place field, or of increased variability in place field positions across traversals. We addressed this question by monitoring CA1 place cell activity, with tetrodes, in control and KO mice lacking the NMDA receptor in this region. In individual crossings of the field, we found no difference between genotypes in place field size; the larger, overall place field size turns out to be a consequence of jitter across trials. We suggest that this jitter reflects a deficit in the matching of current spatial inputs to the stored spatial representation of the track. This is supported by the finding that deficits in place field size and spatial information are rescued by extensive exposure of the mouse to the track, which may echo an increased influence of memory retrieval processes in CA3 on firing in CA1.
Published: 2014

39. How the cerebellum may monitor sensory information for spatial representation

Author: Laure Rondi-Reig, Julie M. Lefort, Anne-Lise Paradis, Benedicte M. Babayan, Christine Tobin, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Sensory processing, cerebellum, Computer science, hippocampus, Cognitive Neuroscience, medicine.medical_treatment, media_common.quotation_subject, Neuroscience (miscellaneous), Posterior parietal cortex, Sensory system, Review Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Navigation function, Perception, medicine, Entorhinal Cortex, Head direction cells, place cells, navigation, sensory processing, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, head direction cells, 030304 developmental biology, media_common, self-motion, 0303 health sciences, Computational model, Novelty, parietal cortex, nervous system, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; The cerebellum has already been shown to participate in the navigation function. We propose here that this structure is involved in maintaining a sense of direction and location during self-motion by monitoring sensory information and interacting with navigation circuits to update the mental representation of space. To better understand the processing performed by the cerebellum in the navigation function, we have reviewed: the anatomical pathways that convey self-motion information to the cerebellum; the computational algorithm(s) thought to be performed by the cerebellum from these multi-source inputs; the cerebellar outputs directed toward navigation circuits and the influence of self-motion information on space-modulated cells receiving cerebellar outputs. This review highlights that the cerebellum is adequately wired to combine the diversity of sensory signals to be monitored during self-motion and fuel the navigation circuits. The direct anatomical projections of the cerebellum toward the head-direction cell system and the parietal cortex make those structures possible relays of the cerebellum influence on the hippocampal spatial map. We describe computational models of the cerebellar function showing that the cerebellum can filter out the components of the sensory signals that are predictable, and provides a novelty output. We finally speculate that this novelty output is taken into account by the navigation structures, which implement an update over time of position and stabilize perception during navigation.
Published: 2014

40. Forebrain-Specific Calcineurin Knockout Selectively Impairs Bidirectional Synaptic Plasticity and Working/Episodic-like Memory

Author: Sumantra Chattarji, Michaela Barbarosie, Tsuyoshi Miyakawa, Benjamin D. Philpot, Susumu Tonegawa, Hongkui Zeng, Mark F. Bear, and Laure Rondi-Reig
Subjects: Male, Patch-Clamp Techniques, Morris water navigation task, Hippocampus, In Vitro Techniques, Biology, Receptors, N-Methyl-D-Aspartate, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Memory, Conditioning, Psychological, Neuroplasticity, Animals, Learning, Protein Isoforms, Maze Learning, In Situ Hybridization, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Neuronal Plasticity, Biochemistry, Genetics and Molecular Biology(all), Calcineurin, Excitatory Postsynaptic Potentials, Long-term potentiation, Mice, Inbred C57BL, Protein Subunits, nervous system, Episodic-like memory, Gene Targeting, Synaptic plasticity, Memory consolidation, Neuroscience, psychological phenomena and processes, 030217 neurology & neurosurgery
Abstract: Calcineurin is a calcium-dependent protein phosphatase that has been implicated in various aspects of synaptic plasticity. By using conditional gene-targeting techniques, we created mice in which calcineurin activity is disrupted specifically in the adult forebrain. At hippocampal Schaffer collateral-CA1 synapses, LTD was significantly diminished, and there was a significant shift in the LTD/LTP modification threshold in mutant mice. Strikingly, although performance was normal in hippocampus-dependent reference memory tasks, including contextual fear conditioning and the Morris water maze, the mutant mice were impaired in hippocampus-dependent working and episodic-like memory tasks, including the delayed matching-to-place task and the radial maze task. Our results define a critical role for calcineurin in bidirectional synaptic plasticity and suggest a novel mechanistic distinction between working/episodic-like memory and reference memory.
Published: 2001

41. Transgenic mice with neuronal overexpression of bcl-2 gene present navigation disabilites in a water task

Author: Jean Mariani, Céline Montécot, Dominique Muller, Jean-Claude Martinou, Laure Rondi-Reig, Jean Caston, and Y. Lemaigre-Dubreuil
Subjects: Central Nervous System, Genetically modified mouse, Programmed cell death, Ratón, Long-Term Potentiation, Central nervous system, Hippocampus, Apoptosis, Mice, Transgenic, Learning Disorders/ genetics, Orientation/ physiology, Mice, Genes, bcl-2/ genetics, Neurons/ metabolism, Orientation, Reaction Time, medicine, Animals, Apoptosis/ genetics, Gene, Behavior, Animal/physiology, Hippocampus/growth & development/metabolism/pathology, Neurons, Reaction Time/genetics, Behavior, Animal, Dentate Gyrus/growth & development/metabolism/pathology, Learning Disabilities, General Neuroscience, Gene Expression Regulation, Developmental, Genes, bcl-2, ddc:616.8, Central Nervous System/ growth & development/metabolism/pathology, Proto-Oncogene Proteins c-bcl-2/genetics, Mice, Transgenic/genetics/ metabolism, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Dentate Gyrus, NMDA receptor, Psychology, Motor learning, Gene Expression Regulation, Developmental/genetics, Neuroscience, Long-Term Potentiation/genetics
Abstract: In the CNS, Bcl-2 is an antiapoptotic gene involved in the regulation of neuronal death. Transgenic mice overexpressing the human gene Bcl-2 (Hu-bcl-2 mice) showed delayed acquisition in two tasks requiring them to find a hidden platform starting from either a random or a constant starting location. The same mice were not deficient in another task requiring them to find a visible platform suggesting that the delay observed was not due to motor, visual or motivational deficits in the water. The delay observed in Hu-bcl-2 mice was more important in the random starting test in which the allocentric demand for navigation was stronger. The results suggested that allocentric navigation is particularly sensitive to abnormal CNS maturation following the overexpression of the bcl-2 gene. The specific deficits (motor learning, fear-related behavior and allocentric navigation) observed in Hu-bcl-2 mice suggest that the regulation of developmental neuronal death is crucial for multisensorial learning and emotional behavior.
Published: 2001

42. Hu-Bcl-2 transgenic mice with supernumerary neurons exhibit timing impairment in a complex motor task

Author: Jean-Claude Martinou, Yolande Lemaigre Dubreuil, Jean Mariani, Laure Rondi-Reig, Ann M. Lohof, Nicole Delhaye-Bouchaud, and Jean Caston
Subjects: Genetically modified mouse, Programmed cell death, Time Factors, Cell, Mice, Transgenic, In Vitro Techniques, Motor Activity, Biology, Synaptic Transmission, Mice, Nerve Fibers, Cerebellum, medicine, Animals, Humans, Supernumerary, Muscle, Skeletal, book, Neurons, General Neuroscience, Developmental cell, Excitatory Postsynaptic Potentials, Electric Stimulation, Motor coordination, Electrophysiology, Motor task, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, nervous system, Neuronal circuits, book.journal, Neuroscience
Abstract: Programmed neuronal cell death is common during development, and is thought to be important in the elimination of errors in axonal projection, cell position and sculpting of neuronal circuits. However, the potential importance of programmed cell death for complex behaviour in the adult animal has never been addressed. We studied motor abilities in a strain of transgenic mice with neuronal overexpression of the human Bcl-2 protein, which have supernumerary neurons due to reduced developmental cell death. Our results show that these mice have a clear deficiency in fine timing of motor coordination without impairment of basic motor functions. This is the first indication that altered developmental cell death and the consequent neuronal surplus can impair complex behaviour in the adult animal.
Published: 1999

43. Overexpression of a Hu-bcl-2 transgene in Lurcher mutant mice delays Purkinje cell death

Author: Jean Mariani, Nicole Delhaye-Bouchaud, Jean-Claude Martinou, Michael W. Vogel, Hadi Shojaeian Zanjani, and Laure Rondi-Reig
Subjects: Male, Programmed cell death, Mutation, Cell Death, Ecology, Ratón, Transgene, Purkinje cell, Mutant, Glutamate receptor, Gene Expression Regulation, Developmental, Lurcher, Biology, medicine.disease_cause, Molecular biology, General Biochemistry, Genetics and Molecular Biology, Genes, bcl-2, Mice, Mice, Neurologic Mutants, Purkinje Cells, medicine.anatomical_structure, Nerve Degeneration, medicine, Animals, Female
Abstract: Cerebellar Purkinje cells in the heterozygous Lurcher mutant undergo cell autonomous degeneration beginning in the second week of postnatal development and becoming almost total around 30-45 days. The Lurcher mutation was recently identified as gain-of-function defect in the delta 2 glutamate receptor causing a constitutive current leak, suggesting that +/Lc Purkinje cells die by an excitotoxic mechanism. In previous studies we have shown that overexpression of bcl-2, a key regulator of cell death, in the heterozygous Lurcher mutant does not prevent +/Lc Purkinje cell death. To investigate further the mechanisms of +/Lc Purkinje cell death, we have crossed +/Lc mutants with a second line of Hu-bcl-2 transgenics (NSE73a) that shows an earlier onset of transgene expression and higher expression levels. Analysis of eight +/Lc-NSE73a mutants (4 at 2 months and 4 at 5-6 months) showed that Hu-bcl-2 overexpression delayed, but ultimately could not prevent +/Lc Purkinje cell death.
Published: 1998

44. staggerer phenotype in retinoid-related orphan receptor α-deficient mice

Author: Constantino Sotelo, Nathalie Auclair, Laure Rondi-Reig, Nicole Delhaye-Bouchaud, Michael Becker-André, Elisabeth André, Markus Steinmayr, Hervé Daniel, François Conquet, Jean Mariani, and Francis Crépel
Subjects: medicine.medical_specialty, Cerebellum, Central nervous system, Receptors, Cytoplasmic and Nuclear, Nerve Tissue Proteins, Biology, Retinal ganglion, Mice, Internal medicine, medicine, Animals, Orphan receptor, Regulation of gene expression, Retina, Multidisciplinary, Behavior, Animal, Nuclear Receptor Subfamily 1, Group F, Member 1, Biological Sciences, Hair follicle, Mice, Mutant Strains, Cell biology, Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, Nuclear receptor, Organ Specificity, Mutation, Trans-Activators
Abstract: Retinoid-related orphan receptor α (RORα) is a member of the nuclear receptor superfamily. To study its physiological role we generated null-mutant mice by targeted insertion of a lacZ reporter gene encoding the enzyme β-galactosidase. In heterozygous RORα +/− mice we found β-galactosidase activity, indicative of RORα protein expression, confined to the central nervous system, skin and testis. In the central nervous system, the RORα gene is expressed in cerebellar Purkinje cells, the thalamus, the suprachiasmatic nuclei, and retinal ganglion cells. In skin, RORα is strongly expressed in the hair follicle, the epidermis, and the sebaceous gland. Finally, the peritubular cells of the testis and the epithelial cells of the epididymis also strongly express RORα. Recently, it was reported that the ataxic mouse mutant staggerer ( sg / sg ) is caused by a deletion in the RORα gene. The analysis of the cerebellar and the behavioral phenotype of homozygous RORα −/− mice proves identity to sg / sg mice. Although the absence of RORα causes dramatic developmental effects in the cerebellum, it has no apparent morphological effect on thalamus, hypothalamus, and retina. Similarly, testis and skin of RORα −/− mice display a normal phenotype. However, the pelage hair of both sg/sg and RORα −/− is significantly less dense and when shaved shows reluctance to regrow.
Published: 1998

45. Inhibition of neuronal (type 1) nitric oxide synthase prevents hyperaemia and hippocampal lesions resulting from kainate-induced seizures

Author: Jacques Seylaz, Véronique Springhetti, Céline Montécot, Laure Rondi-Reig, and Elisabeth Pinard
Subjects: Male, medicine.medical_specialty, Kainic acid, 7-Nitroindazole, Hyperemia, Kainate receptor, Nitric Oxide Synthase Type I, Status epilepticus, Hippocampal formation, Hippocampus, Nitric oxide, chemistry.chemical_compound, Oxygen Consumption, Status Epilepticus, Seizures, Internal medicine, Excitatory Amino Acid Agonists, medicine, Animals, Enzyme Inhibitors, Rats, Wistar, Kainic Acid, Behavior, Animal, biology, General Neuroscience, Electroencephalography, Rats, Nitric oxide synthase, Endocrinology, chemistry, Cerebral blood flow, Cerebrovascular Circulation, Anesthesia, biology.protein, Nitric Oxide Synthase, medicine.symptom
Abstract: The possible roles for nitric oxide produced by neurons in epileptic conditions have been investigated from two different aspects: microcirculation and delayed damage. Our aim was to determine whether the selective inhibition of neuronal (type 1) nitric oxide synthase by 7-nitroindazole, during seizures induced by systemic kainate, modifies hippocampal blood flow and oxygen supply and influences the subsequent hippocampal damage. Experiments were performed in conscious Wistar rats whose electroencephalogram was recorded. 7-Nitroindazole (25 mg/kg, i.p.) or its vehicle was injected 30 min before kainate administration (10 mg/kg, i.p.) and then twice at 1-h intervals. Kainate triggered typical limbic seizures evolving into status epilepticus, identified by uninterrupted electroencephalographic spike activity. The seizures were stopped by diazepam (5 mg/kg, i.p.) after 1 h of status epilepticus. Three types of experiments were performed in vehicle- and 7-nitroindazole-treated rats. (1) Hippocampal nitric oxide synthase activity was measured under basal conditions, at 1 h after the onset of the status epilepticus and at 24 h after its termination ( n =4–6 per group). (2) Hippocampal blood flow and tissue partial pressure of oxygen were measured simultaneously by mass spectrometry for the whole duration of the experiment, while systemic variables and body temperature were monitored ( n =6 per group). (3) Hippocampal damage was revealed by Cresyl Violet staining and evaluated with a lesion score seven days after status epilepticus ( n =12 per group). Hippocampal nitric oxide synthase activity was not significantly modified during status epilepticus or the following day in vehicle-treated rats. In contrast, it was inhibited by 57% in 7-nitroindazole-treated rats, both in basal conditions and after 1 h of status epilepticus, but was not different from its basal level 24 h later. 7-Nitroindazole significantly decreased basal hippocampal blood flow and tissue partial pressure in oxygen by 30% and 35%, respectively without affecting any systemic or thermal variable. During status epilepticus, 7-nitroindazole significantly reduced the increase in hippocampal blood flow by 70% and prevented any increase in the tissue partial pressure of oxygen. Seven days later, the hippocampal damage in the CA1 and CA3 layers was significantly less in 7-nitroindazole-treated rats than in vehicle-treated rats. These results indicate that the inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects neurons from seizure-induced toxicity despite reducing blood flow and oxygen supply to the hippocampus.
Published: 1998

46. Fear decrease in transgenic mice over-expressing bcl-2 in neurons

Author: Nicole Delhaye-Bouchaud, Jean Mariani, Y Lemaigre Dubreuil, Jean-Claude Martinou, Laure Rondi-Reig, and Jean Caston
Subjects: Genetically modified mouse, Cerebellum, medicine.medical_specialty, Enolase, Mice, Transgenic, Biology, Amygdala, Mice, Internal medicine, medicine, Animals, Humans, Maze Learning, Promoter Regions, Genetic, Neurons, Diminution, General Neuroscience, Neophobia, Fear, medicine.disease, Recombinant Proteins, medicine.anatomical_structure, Endocrinology, Proto-Oncogene Proteins c-bcl-2, nervous system, Hypothalamus, Phosphopyruvate Hydratase, Brain size, Exploratory Behavior
Abstract: Neuronal destruction in the amygdala, hypothalamus and cerebellum provokes a diminution in anxiety and neophobia. In transgenic mice that express the human bcl-2 gene under the control of neuron specific enolase promotor (Hu-bcl-2), BCL-2 overexpression reduces the naturally occurring neuronal death, producing an increase of the number of neurons and brain size. Since BCL-2 over-expression has been observed in different parts of the brain and especially in the amygdaloid nuclei, the hypothalamus and the cerebellum, we studied the fear-related behavior of these transgenic mice. Hu-bcl-2 transgenic mice showed a decrease in anxiety and neophobia, indicating that, for this particular behavior, supernumerary neurons elicit the same modification as that observed after neuronal destruction.
Published: 1997

47. T-type channel blockade impairs long-term potentiation at the parallel fiber-Purkinje cell synapse and cerebellar learning

Author: Mariano Casado, Arnaud Arabo, Martijn Schonewille, Romain Ly, Anne Feltz, Clément Léna, Chris I. De Zeeuw, Laure Rondi-Reig, Guy Bouvier, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Fondation pour la Recherche Medicale (FRM)/Universite Pierre et Marie Curie fellowship, Region Ile de France, CNRS, Ecole Normale Superieure [ANR-08-SYSC-005, ANR-09-MNPS-38, ANR-11-BSV4-028, ANR-BLAN-SVSE4-LS-120230-DC/MM/, FRM DEQ20120323730], Dutch Organization for Medical Sciences, Dutch Organization for Life Sciences, Erasmus University Rotterdam Fellowship, Center Neuro-Basic, European Research Council Advanced grant, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Netherlands Institute for Neuroscience (NIN), Neurosciences, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cerebellum, Patch-Clamp Techniques, Eye Movements, Purkinje cell, Long-Term Potentiation, Parallel fiber, Biology, Synapse, 03 medical and health sciences, Calcium Channels, T-Type, Mice, Purkinje Cells, 0302 clinical medicine, Piperidines, medicine, Animals, Learning, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Multidisciplinary, Depolarization, Long-term potentiation, Biological Sciences, Calcium Channel Blockers, medicine.anatomical_structure, Rotarod Performance Test, Synaptic plasticity, Benzamides, Synapses, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Motor learning, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Ca(V)3.1 T-type channels are abundant at the cerebellar synapse between parallel fibers and Purkinje cells where they contribute to synaptic depolarization. So far, no specific physiological function has been attributed to these channels neither as charge carriers nor more specifically as Ca2+ carriers. Here we analyze their incidence on synaptic plasticity, motor behavior, and cerebellar motor learning, comparing WT animals and mice where T-type channel function has been abolished either by gene deletion or by acute pharmacological blockade. At the cellular level, we show that Ca(V)3.1 channels are required for long-term potentiation at parallel fiber-Purkinje cell synapses. Moreover, basal simple spike discharge of the Purkinje cell in KO mice is modified. Acute or chronic T-type current blockade results in impaired motor performance in particular when a good body balance is required. Because motor behavior integrates reflexes and past memories of learned behavior, this suggests impaired learning. Indeed, subjecting the KO mice to a vestibulo-ocular reflex phase reversal test reveals impaired cerebellum-dependent motor learning. These data identify a role of low-voltage activated calcium channels in synaptic plasticity and establish a role for Ca(V)3.1 channels in cerebellar learning.
Published: 2013

48. Explicit memory creation during sleep demonstrates a causal role of place cells in navigation

Author: Karim Benchenane, Marie Masako Lacroix, Gaetan de Lavilléon, Laure Rondi-Reig, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation pour la Recherche Medicale, France [DEQ20120323730], National Agency for Research, France [ANR-REG-071220-01-01], CNRS: Programmes Interdisciplinaires de Recherche (Neuro-IC), ATIP-Avenir, city of Paris, program Investissements d'Avenir [ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02], Ministere de l'Enseignement Superieur et de la Recherche, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Neurosciences Paris Seine (NPS)
Subjects: Male, Patch-Clamp Techniques, Place cell, Hippocampus, Hippocampal formation, Spatial memory, Mice, Reward, Explicit memory, Animals, Humans, CA1 Region, Hippocampal, Spatial Memory, Cognitive map, Behavior, Animal, General Neuroscience, Medial Forebrain Bundle, Electric Stimulation, Electrodes, Implanted, Mice, Inbred C57BL, Memory consolidation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep (system call), Psychology, Sleep, Neuroscience, Goals, Spatial Navigation
Abstract: International audience; Hippocampal place cells assemblies are believed to support the cognitive map, and their reactivations during sleep are thought to be involved in spatial memory consolidation. By triggering intracranial rewarding stimulations by place cell spikes during sleep, we induced an explicit memory trace, leading to a goal-directed behavior toward the place field. This demonstrates that place cells' activity during sleep still conveys relevant spatial information and that this activity is functionally significant for navigation.
Published: 2013

49. A Navigation Analysis Tool (NAT) to assess spatial behavior in open-field and structured mazes

Author: Laure Rondi-Reig, Angelo Arleo, Celine Fouquet, Julie M. Lefort, Eric Burguière, Frédéric Jarlier, Géraldine H. Petit, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), ANR Project EvoNeuro [ANR-09-EMER-005-01], GIS Program `Longevity' [SRI20001117030, L0201], ACI Program `Integrative and Computational Neuroscience' [NIC 0083], Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Time Factors, Computer science, Data management, Context (language use), Personalization, Software portability, Software, Human–computer interaction, Automated statistical analysis, Animals, Humans, Decision point analysis, Maze Learning, JAVA graphical user interface, Graphical user interface, MySQL relational database, MATLAB analysis toolbox, business.industry, General Neuroscience, Modular design, Open source software, Spatial behavior, Space Perception, Navigation strategies, Exploratory Behavior, Database Management Systems, Goal-oriented behavior, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], User interface, business, Goals
Abstract: International audience; Spatial navigation calls upon mnemonic capabilities (e.g. remembering the location of a rewarding site) as well as adaptive motor control (e.g. fine tuning of the trajectory according to the ongoing sensory context). To study this complex process by means of behavioral measurements it is necessary to quantify a large set of meaningful parameters on multiple time scales (from milliseconds to several minutes), and to compare them across different paradigms. Moreover, the issue of automating the behavioral analysis is critical to cope with the consequent computational load and the sophistication of the measurements. We developed a general purpose Navigation Analysis Tool (NAT) that provides an integrated architecture consisting of a data management system (implemented in MySQL), a core analysis toolbox (in MATLAB), and a graphical user interface (in JAVA). Its extensive characterization of trajectories over time, from exploratory behavior to goal-oriented navigation with decision points using a wide range of parameters, makes NAT a powerful analysis tool. In particular, NAT supplies a new set of specific measurements assessing performances in multiple intersection mazes and allowing navigation strategies to be discriminated (e.g. in the starmaze). Its user interface enables easy use while its modular organization provides many opportunities of extension and customization. Importantly, the portability of NAT to any type of maze and environment extends its exploitation far beyond the field of spatial navigation.
Published: 2013

50. The cerebellum: a new key structure in the navigation system

Author: Laure Rondi-Reig, Julie M. Lefort, Christelle Rochefort, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation pour la Recherche Medicale, France [DEQ20120323730,], National Agency for Research, France [ANR-REG-071220-01-01], Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cerebellum, cerebellum, hippocampus, Cognitive Neuroscience, path integration, Neuroscience (miscellaneous), Spatial Behavior, Parallel fiber, Review Article, Spatial memory, lcsh:RC321-571, Purkinje Cells, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neural Pathways, Neuroplasticity, medicine, Animals, Humans, place cells, navigation, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, self-motion, Vestibular system, 0303 health sciences, Neuronal Plasticity, Spatial cognition, Sensory Systems, medicine.anatomical_structure, Eyeblink conditioning, Space Perception, spatial representation, LTD, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Motor learning, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Early investigations of cerebellar function focused on motor learning, in particular on eyeblink conditioning and adaptation of the vestibulo-ocular reflex, and led to the general view that cerebellar long-term depression (LTD) at parallel fiber (PF)-Purkinje cell (PC) synapses is the neural correlate of cerebellar motor learning. Thereafter, while the full complexity of cerebellar plasticities was being unraveled, cerebellar involvement in more cognitive tasks-including spatial navigation-was further investigated. However, cerebellar implication in spatial navigation remains a matter of debate because motor deficits frequently associated with cerebellar damage often prevent the dissociation between its role in spatial cognition from its implication in motor function. Here, we review recent findings from behavioral and electrophysiological analyses of cerebellar mutant mouse models, which show that the cerebellum might participate in the construction of hippocampal spatial representation map (i.e., place cells) and thereby in goal-directed navigation. These recent advances in cerebellar research point toward a model in which computation from the cerebellum could be required for spatial representation and would involve the integration of multi-source self-motion information to: (1) transform the reference frame of vestibular signals and (2) distinguish between self- and externally-generated vestibular signals. We eventually present herein anatomical and functional connectivity data supporting a cerebello-hippocampal interaction. Whilst a direct cerebello-hippocampal projection has been suggested, recent investigations rather favor a multi-synaptic pathway involving posterior parietal and retrosplenial cortices, two regions critically involved in spatial navigation.
Published: 2013

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