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

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37 results on '"Laure Rondi-Reig"'

1. 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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2. 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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3. 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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4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. [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

16. 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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17. 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

18. 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

19. 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

20. 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

21. 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

22. 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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23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. Temporal Order Memory Assessed during Spatiotemporal Navigation As a Behavioral Cognitive Marker for Differential Alzheimer's Disease Diagnosis

Author: Bruno Dubois, Laure Rondi-Reig, Leonardo Cruz de Souza, Kinga Igloi, Virginie Bellassen, 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 Recherche Medicale [DLC20060206428], Agence Nationale de la Recherche (ANR) [07-JCJC-0108-01], Universite Pierre et Marie Curie (BQR), 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 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, Time Factors, Spatial Behavior, Normal aging, Disease, Neuropsychological Tests, Spatial memory, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Experimental testing, Alzheimer Disease, Memory, medicine, Humans, Episodic memory, Aged, 030304 developmental biology, Aged, 80 and over, Memory Disorders, 0303 health sciences, General Neuroscience, Neuropsychology, Cognition, Articles, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Frontotemporal Lobar Degeneration, Cognition Disorders, Psychology, Neuroscience, Photic Stimulation, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract: Episodic memory impairment is a hallmark for early diagnosis of Alzheimer's disease. Most actual tests used to diagnose Alzheimer's disease do not assess the spatiotemporal properties of episodic memory and lead to false-positive or -negative diagnosis. We used a newly developed, nonverbal navigation test for Human, based on the objective experimental testing of a spatiotemporal experience, to differentially Alzheimer's disease at the mild stage (N= 16 patients) from frontotemporal lobar degeneration (N= 11 patients) and normal aging (N= 24 subjects). Comparing navigation parameters and standard neuropsychological tests, temporal order memory appeared to have the highest predictive power for mild Alzheimer's disease diagnosis versus frontotemporal lobar degeneration and normal aging. This test was also nonredundant with classical neuropsychological tests. As a conclusion, our results suggest that temporal order memory tested in a spatial navigation task may provide a selective behavioral marker of Alzheimer's disease.
Published: 2012

34. Cerebellum Shapes Hippocampal Spatial Code

Author: Bruno Poucet, Etienne Save, Christelle Rochefort, Marion André, Laure Rondi-Reig, Arnaud Arabo, Max-Planck-Institut für Molekulare Genetik (MPIMG), Max-Planck-Gesellschaft, Laboratory of Animal Behaviour, Freie Universität Berlin, École supérieure du professorat et de l'éducation - Languedoc-Roussillon (ESPE Languedoc-Roussillon), Université de Montpellier (UM), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des processus adaptatifs (NPA), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cerebellum, Transgene, Place cell, Mice, Transgenic, Motor Activity, Hippocampal formation, Biology, Spatial memory, Mice, Purkinje Cells, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Orientation, Path integration, medicine, Animals, CA1 Region, Hippocampal, Protein Kinase C, Protein kinase C, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Long-Term Synaptic Depression, Pyramidal Cells, [SCCO.NEUR]Cognitive science/Neuroscience, Darkness, Spatial code, Mice, Inbred C57BL, medicine.anatomical_structure, Space Perception, Cues, Neuroscience, 030217 neurology & neurosurgery
Abstract: Spatial representation is an active process that requires complex multimodal integration from a large interacting network of cortical and subcortical structures. We sought to determine the role of cerebellar protein kinase C (PKC)-dependent plasticity in spatial navigation by recording the activity of hippocampal place cells in transgenic L7PKCI mice with selective disruption of PKC-dependent plasticity at parallel fiber-Purkinje cell synapses. Place cell properties were exclusively impaired when L7PKCI mice had to rely on self-motion cues. The behavioral consequence of such a deficit is evidenced here by selectively impaired navigation capabilities during a path integration task. Together, these results suggest that cerebellar PKC-dependent mechanisms are involved in processing self-motion signals essential to the shaping of hippocampal spatial representation.
Published: 2011

35. Modeling cerebellar learning for spatial cognition

Author: Jean-Baptiste Passot, Angelo Arleo, and Laure Rondi-Reig
Subjects: Cerebellum, General Neuroscience, lcsh:QP351-495, Genetic data, Spatial cognition, lcsh:RC321-571, Cellular and Molecular Neuroscience, lcsh:Neurophysiology and neuropsychology, medicine.anatomical_structure, medicine, Spatial learning, Psychology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Neuroscience
Abstract: Recent experimental findings have begun to unravel the implication of the cerebellum in high-level functions such as spatial cognition [1,2]. We focus on behavioral genetic data showing that L7-PKCI mice (lacking LTD at parallel fibers-Purkinje cell synapses) have a spatial learning impairment in the Morris Watermaze (MWM), whereas they exhibit normal performances in the Starmaze, a paradigm that reduces the procedural demand of the task [3]. These results suggest that cerebellar learning may prominently contribute to the procedural component of spatial learning [3].
Published: 2009

36. Early detection of age-related memory deficits in individual mice

Author: Jean Mariani, Géraldine H. Petit, Alexandra Auffret, E. Gaillard, Laure Rondi-Reig, Catherine Rovira, Celine Fouquet, Neurobiologie des processus adaptatifs (NPA), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Aging, Long-Term Potentiation, Biophysics, Early detection, Action Potentials, Audiology, Hippocampal formation, In Vitro Techniques, Task (project management), Developmental psychology, Mice, Discrimination, Psychological, Age related, medicine, Animals, Maze Learning, Neurons, Analysis of Variance, Memory Disorders, Chi-Square Distribution, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, Age Factors, Brain, Excitatory Postsynaptic Potentials, Cognition, Electric Stimulation, Mice, Inbred C57BL, Disease Models, Animal, Space Perception, Neurology (clinical), Geriatrics and Gerontology, Cues, Psychology, Developmental Biology
Abstract: International audience; To date, no consensus has been reached concerning the age of the earliest onset of age-related cognitive deficits in rodents. Our aim was to develop a behavioral model allowing early and individual detection of age-related cognitive impairments. We tested young (3 months), middle-aged (10 months) and aged (17 months) C57Bl/6 mice in the starmaze, a task allowing precise analysis of the search pattern of mice via standardized calculation of two navigation indices. We performed mouse-per-mouse analyses and compared each mouse's performance to a threshold based on young mice's performances. Using this method we identified impaired mice from the age of 10 months old. Their deficits were independent of any sensorimotor dysfunctions and were associated with an alteration of the maintenance of the hippocampal CA1 late-LTP. This study develops reliable methodology for early detection of age-related memory disorders and provides evidence that memory can decline in some individuals as early as from the age of 10 months.
Published: 2009

37. To die or not to die, does it change the function? Behavior of transgenic mice reveals a role for developmental cell death

Author: Jean Mariani and Laure Rondi-Reig
Subjects: Genetically modified mouse, Male, Programmed cell death, Ratón, Apoptosis, Mice, Transgenic, Biology, Anxiety, Nervous System Malformations, Mice, medicine, Animals, book, Gene, Neurons, Memory Disorders, Learning Disabilities, General Neuroscience, Developmental cell, Brain, Gene Expression Regulation, Developmental, Hypertrophy, Up-Regulation, Motor Skills Disorders, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, book.journal, Female, Neuron, medicine.symptom, Neuroscience, Function (biology)
Abstract: In humans, perturbations in the developmental neuronal death leading to an excess of neurons could be associated with developmental neuropsychiatric disorders. Hu-bcl-2 transgenic mice appear to be a valuable tool to study the functional role of developmental programmed cell death. Indeed, the over-expression of the anti-apoptotic gene bcl-2 decreases developmental neuronal death and Hu-bcl-2 mice present supernumerary neurons in several brain regions. A detailed behavioral analysis of these mice revealed selective deficits. Hu-bcl-2 mice have normal vision, general activity and motor skills. Only the most complex behavior like anxiety and learning abilities are impaired in these mice.
Published: 2002

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