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In this study, we measured neuronal activation in the primary somatosensory area (S1) and Brodmann area 3 (BA3) using 3T functional magnetic resonance imaging (fMRI) while presenting a 250-Hz high-frequency vibrational stimulus to each of three phalanges (distal, intermediate, and proximal) of four fingers of the right hand (index, middle, ring, and little). We compared the nerve activation area between each finger and each phalange. Ten healthy male college students (26.6 &plusmn, 2.5 years old) participated in this study. One session consisted of three blocks: a rest (30 s), stimulation (30 s), and response phase (9 s). In the rest phase, the vibrational stimulus was not presented. In the stimulation phase, the vibrational stimulation was presented at any one of the three phalanges of the selected finger. In the response phase, subjects were instructed to press a button corresponding to the phalange that they thought had received the vibration. The subtraction method was used to extract the activation area. The activation area in the S1 was the largest when the little finger was stimulated (for the finger comparison), and largest when the second phalange was stimulated (for the phalange comparison). The BA3 showed similar trends, and there was no statistically significant difference.

Sleep supports the consolidation of newly encoded memories, leading to the strengthening, stabilization, and integration of new memories into long-term memory. These processes are assumed to rely on the reactivation (replay) of neuronal activation patterns elicited during learning. In this chapter, we discuss “cued memory reactivation” as an exciting novel approach to manipulate memory consolidation during sleep externally via learning-associated reminder cues. We describe typical experimental paradigms of cued memory reactivation during sleep and give a brief historical overview of this evolving research field. We further examine the effects of cued memory reactivation on different types of memory and consider the efficacy of different sensory cueing modalities (e.g., olfactory and auditory). We then discuss potential mechanisms, including neuronal replay, involved brain areas, neuronal oscillations, and neurotransmitters. Finally, we outline possible applications in the home setting and in the clinical field and examine open questions and directions for future research.

This study examined the interaction between polarity and electrode-activation order on loudness in cochlear implant users. Pulses were presented with the polarity of the leading phase alternating or constant across channels. Electrode-activation order was either consecutive or staggered. Staggered electrode-activation orders required less current for equal loudness than consecutive orders with constant polarity. Consecutive electrode-activation orders required less current than staggered orders with alternating polarity. The results support the hypothesis that crosstalk between channels can interfere with or facilitate neuronal activation depending on polarity.

In this paper, a new vector phase diagram differentiating the initial decreasing phase (i.e. initial dip) and the delayed hemodynamic response (HR) phase of oxy-hemoglobin changes ([Formula: see text]HbO) of functional near-infrared spectroscopy (fNIRS) is developed. The vector phase diagram displays the trajectories of [Formula: see text]HbO and deoxy-hemoglobin changes ([Formula: see text]HbR), as orthogonal components, in the [Formula: see text]HbO–[Formula: see text]HbR polar coordinates. To determine the occurrence of an initial dip, dual threshold circles (an inner circle from the resting state, an outer circle from the peak values of the initial dip and the main HR) are incorporated into the phase diagram for making decisions. The proposed scheme is then applied to a brain–computer interface scheme, and its performance is evaluated in classifying two finger tapping tasks (right-hand thumb and little finger) from the left motor cortex. Three gamma functions are used to model the initial dip, the main HR, and the undershoot in generating the designed HR function. In classifying two tapping tasks, the signal mean and signal minimum values during 0–2.5[Formula: see text]s, as features of initial dip, are used. The linear discriminant analysis was utilized as a classifier. The experimental results show that the active brain locations of the two tasks were quite distinctive ([Formula: see text]), and moreover, spatially specific if using the initial dip map at 4[Formula: see text]s in comparison to the map of HRs at 14[Formula: see text]s. Also, the average classification accuracy was improved from 59% to 74.9% when using the phase diagram of dual threshold circles.

Prairie voles are socially monogamous mammals that form pair bonds and display paternal care. This study was focused on the male prairie vole's neuronal responses to infant-related odors. Using the fos protein as a measure of neuronal activation, we examined the brain responses of males to infant-related odors. Prior to testing, the subjects had cohabited for two weeks with either a male sibling (Male-Cohabited) or an unrelated female (Female-Cohabited). Given that paternal behavior of male prairie voles is enhanced after two-weeks of cohabitation with a mate, we hypothesized that fos activation in brain regions involved in caring must be increased in response to infants or their odors but not in response to water or sub-adult odors. To test this hypothesis, we analyzed the pattern of fos expression in the ventral tegmental area (VTA) and the bed nucleus of the stria terminals (BNST) two hours after Male-Cohabited and Female-Cohabited males were exposed to either two live infants or to odors of infants, sub-adults or water. Results showed differences in fos expression within the VTA between Male-Cohabited and Female-Cohabited subjects that were exposed to infants and infant odors. The type of cohabitation had no effect on fos expression within the BNST, but the pattern of fos activation in this region differed by the type of odor to which the subjects were exposed. Together, the data indicate that female sensory cues during post-mating cohabitation may be processed within the VTA to direct the male prairie vole's responses towards infants.

Matrix metalloproteinase-9 (Mmp-9) is involved in different general and cell-type-specific processes, both in neuronal and non-neuronal cells. Moreover, it is implicated in an induction or progression of various human disorders, including diseases of the central nervous system. Mechanisms regulating activity-driven Mmp-9 expression in neurons are still not fully understood. Here, we show that stabilization of Mmp-9 mRNA is one of the factors responsible for the neuronal activity-evoked upregulation of Mmp-9 mRNA expression in hippocampal neurons. Furthermore, we demonstrate that the molecular mechanism related to this stabilization is dependent on the neuronal seizure-triggered transiently increased binding of the mRNA stability-inducing protein, HuR, to ARE1 and ARE4 motifs of the 3'UTR for Mmp-9 mRNA as well as the stably augmented association of another mRNA-stabilizing protein, HuB, to the ARE1 element of the 3'UTR. Intriguingly, we demonstrate further that both HuR and HuB are crucial for an incidence of Mmp-9 mRNA stabilization after neuronal activation. This study identifies Mmp-9 mRNA as the first HuB target regulated by mRNA stabilization in neurons. Moreover, these results are the first to describe an existence of HuR-dependent mRNA stabilization in neurons of the brain.

International audience; Episodic memory decline is one of the earlier deficits occurring during normal aging in humans. The question of spatial versus non-spatial sensitivity to age-related memory decline is of importance for a full understanding of these changes. Here, we characterized the effect of normal aging on both non-spatial (object) and spatial (object location) memory performances as well as on associated neuronal activation in mice. Novel-object (NOR) and object-location (OLR) recognition tests, respectively assessing the identity and spatial features of object memory, were examined at different ages. We show that memory performances in both tests were altered by aging as early as 15 months of age: NOR memory was partially impaired whereas OLR memory was found to be fully disrupted at 15 months of age. Brain activation profiles were assessed for both tests using immunohistochemical detection of c-Fos (neuronal activation marker) in 3and 15 month-old mice. Normal performances in NOR task by 3 month-old mice were associated to an activation of the hippocampus and a trend towards an activation in the perirhinal cortex, in a way that did significantly differ with 15 month-old mice. During OLR task, brain activation took place in the hippocampus in 3 month-old but not significantly in 15 month-old mice, which were fully impaired at this task. These differential alterations of the object- and object-location recognition memory may be linked to differential alteration of the neuronal networks supporting these tasks.

An impediment to a mechanistic understanding of how some species sense the geomagnetic field (“magnetoreception”) is the lack of vertebrate genetic models that exhibit well-characterized magnetoreceptive behavior and are amenable to whole-brain analysis. We investigated the genetic model organisms zebrafish and medaka, whose young stages are transparent and optically accessible. In an unfamiliar environment, adult fish orient according to the directional change of a magnetic field even in darkness. To enable experiments also in juveniles, we applied slowly oscillating magnetic fields, aimed at generating conflicting sensory inputs during exploratory behavior. Medaka (but not zebrafish) increase their locomotor activity in this assay. Complementary brain activity mapping reveals neuronal activation in the lateral hindbrain during magnetic stimulation. These comparative data support magnetoreception in teleosts, provide evidence for a light-independent mechanism, and demonstrate the usefulness of zebrafish and medaka as genetic vertebrate models for studying the biophysical and neuronal mechanisms underlying magnetoreception., Advances in animal magnetoreception have been limited by a lack of tractable vertebrate laboratory models. Here, the authors demonstrate light-independent magnetoreception in mature zebrafish and medaka, as well as magnetosensitive locomotion in juvenile medaka associated with neuronal activation in the lateral hindbrain.

Amphibians are central to discussions of vertebrate evolution because they represent the transition from aquatic to terrestrial life, a transition with profound consequences for the selective pressures shaping brain evolution. Spatial navigation is one class of behavior that has attracted the interest of comparative neurobiologists because of the relevance of the medial pallium/hippocampus, yet, surprisingly, in this regard amphibians have been sparsely investigated. In the current study, we trained toads to locate a water goal relying on the boundary geometry of a test environment (Geometry-Only) or boundary geometry coupled with a prominent, visual feature cue (Geometry-Feature). Once learning had been achieved, the animals were given one last training session and their telencephali were processed for c-Fos activation. Compared to control toads exposed to the test environment for the first time, geometry-only toads were found to have increased neuronal labeling in the medial pallium, the presumptive hippocampal homologue, while geometry-feature toads were found to have increased neuronal labeling in the medial, dorsal, and lateral pallia. The data indicate medial pallial participation in guiding navigation by environmental geometry and lateral, and to a lesser extent dorsal, pallial participation in guiding navigation by a prominent visual feature. As such, participation of the medial pallium/hippocampus in spatial cognition appears to be a conserved feature of terrestrial vertebrates even if their life history is still tied to water, a brain-behavior feature seemingly at least as ancient as the evolutionary transition to life on land.

Summary The effects of physical training on hypothalamic activation after exercise and their relationship with heat dissipation were investigated. Following 8 weeks of physical training, trained (TR, n = 9) and untrained (UN, n = 8) Wistar rats were submitted to a regimen of incremental running until fatigue while body and tail temperatures were recorded. After exercise, hypothalamic c-Fos immunohistochemistry analysis was performed. The workload, body-heating rate, heat storage and body temperature threshold for cutaneous vasodilation were calculated. Physical training increased the number of c-Fos immunoreactive neurons in the paraventricular, medial preoptic and median preoptic nucleus by 112%, 90% and 65% (P

Nutritional fat is one of the most controversial topics in nutritional research, particularly against the background of obesity. Studies investigating fat taste perception have revealed several associations with sensory, genetic, and personal factors (e.g. BMI). However, neuronal activation patterns, which are known to be highly sensitive to different tastes as well as to BMI differences, have not yet been included in the scheme of fat taste perception. We will therefore provide a comprehensive survey of the sensory, genetic, and personal factors associated with fat taste perception and highlight the benefits of applying neuroimaging research. We will also give a critical overview of studies investigating sensory fat perception and the challenges resulting from multifaceted methodological approaches. In conclusion, we will discuss a multifactorial approach to fat perception to gain a better understanding of the underlying mechanisms that cause varying fat sensitivity which could be responsible for overeating. Such knowledge might be beneficial in new treatment strategies for obesity and overweight.

The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K(+) concentration ([K(+)]e) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K(+)]e and ECS volume affect the velocity, frequency, and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4(+/+)) and AQP4-deficient (AQP4(-/-)) mice. In contrast to initial expectations, both the velocity and the frequency of CSD were significantly reduced in AQP4(-/-) mice when compared with AQP4(+/+) mice, by 22% and 32%, respectively. Measurement of [K(+)]e with K(+)-selective microelectrodes demonstrated an increase to ∼35 mM during spreading depolarizations in both AQP4(+/+) and AQP4(-/-) mice, but the rates of [K(+)]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4(-/-) mice. ECS volume fraction measured by tetramethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4(+/+) mice, and 0.23 to 0.063 in AQP4(-/-) mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4(-/-) mice was primarily a consequence of the slowed increase in [K(+)]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K(+)]e and ECS volume dynamics accelerate CSD propagation.

Tissue plasminogen activator (tPA) is known to play physiologically and pathologically crucial roles in the central nervous system. However, it is still obscure whether it affects social behavior. We investigated social behavior and neuronal activation after social stimulation in tPA knockout (KO) mice. In a resident-intruder test, the latency to the first contact was significantly delayed in tPA KO mice compared with that in tPA heterogenic (Het) mice. However, tPA KO mice spent significantly more time undertaking active behavior than tPA Het mice did. In a sociability test, tPA KO mice significantly spent more time and walked a greater distance in the chamber containing an empty cage than tPA Het mice. Furthermore, tPA KO mice approached an empty cage more frequently than tPA Het mice did. In a social novelty test, there was no difference in the duration spent sniffing a stimulator mouse between genotypes. However, tPA KO mice approached even a familiar mouse more frequently than tPA Het mice did. tPA KO mice spent similar durations in a chamber containing a familiar mouse and that containing an unfamiliar mouse, and tPA KO mice walked a significantly greater distance in the former chamber than tPA Het mice did. Furthermore, at the cingulate and prelimbic cortices, the number of cFos-positive cells was significantly increased in tPA KO mice compared with that in tPA Het mice after social stimulation. Our results suggest that tPA modulates emotion in a social context through the function of the prefrontal cortex.

We consider recent developments in Bayesian spatiotemporal models for detecting neuronal activation in fMRI experiment. A Bayesian approach typically results in complicated posterior distributions that can be of enormous dimension for a whole-brain analysis, thus posing a formidable computational challenge. Recently developed Bayesian approaches to detecting local activation have proved computationally efficient while requiring few modeling compromises. We review two such methods and implement them on a data set from the Human Connectome Project in order to show that, contrary to popular opinion, careful implementation of Markov chain Monte Carlo methods can be used to obtain reliable results in a matter of minutes.

Pain is often thought of as a sensory experience, but it has a distinct emotional aspect to it. This is no more evident than the thoughts and feelings that we experience when we watch another person in pain. The observation of another person in pain elicits similar emotional responses as the firsthand experience of pain and as such, pain is often used to measure empathy. Here, we consider empathy for pain as it relates to neuronal activation patterns in humans, while also examining parallel findings in rodents. The use of both human and rodent models to understand the core components of pain empathy is discussed, as is the wider concept of pain in the social neurosciences. The existence of parallels between humans and rodents suggests that translational studies are possible within this domain and only with such studies we will be able to fully appreciate the neuronal complexities of empathy.

It has been suggested that the dentate gyrus, particularly its new neurons generated via adult neurogenesis, is involved in memory acquisition and recall. Here, we trained rats in two types of Morris water maze tasks that are differentially associated with these two memory processes, and examined whether new neurons are differently affected by the two tasks performed during the second week of neuronal birth. Our results indicate that the task involving more opportunities to acquire new information better supports the survival of new neurons. Further, we assessed whether the two tasks differentially induce the expression of an immediate early gene, Zif268, which is known to be induced by neuronal activation. While the two tasks differentially induce Zif268 expression in the dentate gyrus, the proportions of new neurons activated were similar between the two tasks. Thus, we conclude that while the two tasks differentially activate the dentate gyrus, the task involving more opportunities for memory acquisition during the second week of the birth of new neurons better promotes the survival of the new neurons. © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License.

The majority of 20th century investigations into anesthetic effects on the nervous system have used electrophysiology. Yet some fundamental limitations to electrophysiologic recordings, including the invasiveness of the technique, the need to place (potentially several) electrodes in every site of interest, and the difficulty of selectively recording from individual cell types, have driven the development of alternative methods for detecting neuronal activation. Two such alternative methods with cellular scale resolution have matured in the last few decades and will be reviewed here: the transcription of immediate early genes, foremost c-fos, and the influx of calcium into neurons as reported by genetically encoded calcium indicators, foremost GCaMP6. Reporters of c-fos allow detection of transcriptional activation even in deep or distant nuclei, without requiring the accurate targeting of multiple electrodes at long distances. The temporal resolution of c-fos is limited due to its dependence upon the detection of transcriptional activation through immunohistochemical assays, though the development of RT-PCR probes has shifted the temporal resolution of the assay when tissues of interest can be isolated. GCaMP6 has several isoforms that trade-off temporal resolution for signal to noise, but the fastest are capable of resolving individual action potential events, provided the microscope used scans quickly enough. GCaMP6 expression can be selectively targeted to neuronal populations of interest, and potentially thousands of neurons can be captured within a single frame, allowing the neuron-by-neuron reporting of circuit dynamics on a scale that is difficult to capture with electrophysiology, as long as the populations are optically accessible.

It is now possible to simultaneously record activity from hundreds of neurons. In some simple organisms such as nematode C. elegans, whole brain imaging with single neuron resolution has been successfully performed. Here we show how such complex datasets can be used to generate quantitative models of the nervous system at the behaviorally-relevant scale. Our model predicts the timing of changes in locomotor direction at least 15 seconds prior to the event. These predictions are valid for individual instances of locomotion and can be applied across individuals including those not used in model construction. In addition, the model predicts behavioral dwell time statistics, sequences of behaviors, and neuronal activation. To develop this model we extracted loops in the trajectories spanned by neuronal activity using novel methodology. The model uses only two variables: the identity of the loop and the phase along it. Current values of these macroscopic variables predict subsequent behaviors. Remarkably, our model based on macroscopic variables succeeds despite consistent differences in activation of individual neurons and neuronal populations between different C. elegans. Thus, our theoretical framework reconciles the variability of neuronal activation amongst individuals with global dynamics that operate universally.

Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand–receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure–activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3.

International audience; While the neuronal activation in the medial frontal cortex is thought to reflect higher-order evaluation processes of reward prediction errors when a reward deviates from our expectation, there is increasing evidence that the medial frontal activity might express prediction errors in general. However, given that several studies examined the medial frontal event-related potentials (ERPs) by comparing signals triggered by different stimuli and different anticipations, it remains an open question whether the medial frontal signals are sensitive to the valence of prediction errors. Here we orthogonally manipulated expectation magnitude (i.e., large/small expectation) and expectation confirmation (i.e., fulfilled/violated expectation) in a target detection task with rewards. We found that the medial frontal ERPs were more negative-going for unexpected outcomes in comparison with expected outcomes, regardless of whether a large/small reward was expected. The result supports the idea that the medial frontal signals express prediction errors in general regardless of their valence.

Carnosine (β-Ala-l-His), an imidazole dipeptide, is known to have many functions. Recently, we demonstrated in a double-blind randomized controlled trial that carnosine is capable of preserving cognitive function in elderly people. In the current study, we assessed the ability of carnosine to activate the brain, and we tried to clarify the molecular mechanisms behind this activation. Our results demonstrate that carnosine permeates the blood brain barrier and activates glial cells within the brain, causing them to secrete neurotrophins, including BDNF and NGF. These results point to a novel mechanism of carnosine-induced neuronal activation. Our results suggest that carnosine should be recognized as a functional food factor that helps achieve anti-brain aging.

Humans are arguably the most complex organisms present on Earth with their ability to imagine, create, and problem solve. As underlying mechanisms enabling these capacities reside in the brain, it is not surprising that the brain has undergone an extraordinary increase in size and complexity within the last few million years. Human induced pluripotent stem cells (hiPSCs) can be differentiated into many cell types that were virtually inaccessible historically, such as neurons. Here, we used hiPSC-derived neurons to investigate the cellular response to activation at the transcript level. Neuronal activation was performed with potassium chloride (KCl) and its effects were assessed by RNA sequencing. Our results revealed the involvement of long non-coding RNAs and human-specific genetic variants in response to neuronal activation and help validate hiPSCs as a valuable resource for the study of human neuronal networks. In summary, we find that genes affected by KCl-triggered activation are implicated in pathways that drive cell proliferation, differentiation, and the emergence of specialized morphological features. Interestingly, non-coding RNAs of various classes are amongst the most highly expressed genes in activated hiPSC-derived neurons, thus suggesting these play crucial roles in neural pathways and may significantly contribute to the unique functioning of the human brain.

Despite the discovery of striosomes several decades ago, technical difficulties have hampered the study of their functions. Here we used 2-photon calcium imaging in neuronal birthdate-labeled Mash1-CreER mice to image simultaneously the activity of striosomal and matrix neurons in vivo. We report that with this method we can visually identify circumscribed zones of neuropil that correspond to striosomes as verified in immunostained sections. We find that striosomal neurons, relative to matrix neurons, preferentially encode reward-predicting cues, and that their activity contains more information about expected outcome. These characteristics emerge during training and further strengthen during overtraining. Both striatal compartments are active similarly after reward delivery, firing at neuron-specific times during or after consummatory licking. Finally, we find that immediate reward history strongly modulates neuronal activation in the next trial, especially in matrix neurons. These results suggest that striosomes and matrix have distinct functions in relation to reinforcement learning.

Seizure-induced increase in ΔFosB expression reduces calbindin-28k and might explain cognitive impairments in seizure disorders.

Glutamate is the major excitatory neurotransmitter in the human brain and has a central role in both intrinsic and stimulus-induced activity. We conducted a study in a cohort of healthy, male volunteers in which glutamate levels were measured in the posterior cingulate cortex (PCC) using 1H magnetic resonance spectroscopy at 3T. The advantages of simultaneous electroencephalography and magnetic resonance imaging (EEG-MRI) were exploited and the subjects were measured in the same session and under the same physiological conditions. Diffusion tensor imaging (DTI), functional MRI (fMRI) and EEG were measured in order to investigate the functional and microstructural correlates of glutamate. The concentration of glutamate (institute units) was calculated and those values were tested for correlation with the metrics of resting state fMRI, DTI, and EEG electrical sources. Our results showed that the concentration of glutamate in the PCC had a significant negative correlation with the tissue mean diffusivity in the same area. The analysis of resting state networks did not show any relationship between the concentration of glutamate and the intrinsic activity of the resting state networks. The concentration of glutamate showed a positive correlation with the electrical generators of α-1 frequency and a negative correlation with the generators of α-2 and β-1 electrical generators. © 2017 Wiley Periodicals, Inc.

Glutamate is the major excitatory neurotransmitter in the human brain and has a central role in both intrinsic and stimulus-induced activity. We conducted a study in a cohort of healthy, male volunteers in which glutamate levels were measured in the posterior cingulate cortex (PCC) using 1H magnetic resonance spectroscopy at 3T. The advantages of simultaneous electroencephalography and magnetic resonance imaging (EEG-MRI) were exploited and the subjects were measured in the same session and under the same physiological conditions. Diffusion tensor imaging (DTI), functional MRI (fMRI) and EEG were measured in order to investigate the functional and microstructural correlates of glutamate. The concentration of glutamate (institute units) was calculated and those values were tested for correlation with the metrics of resting state fMRI, DTI, and EEG electrical sources. Our results showed that the concentration of glutamate in the PCC had a significant negative correlation with the tissue mean diffusivity in the same area. The analysis of resting state networks did not show any relationship between the concentration of glutamate and the intrinsic activity of the resting state networks. The concentration of glutamate showed a positive correlation with the electrical generators of α-1 frequency and a negative correlation with the generators of α-2 and β-1 electrical generators. © 2017 Wiley Periodicals, Inc.

Resistin and leptin are adipokines which act in the brain to regulate metabolic and cardiovascular functions which in some instances are similar, suggesting activation of some common brain pathways. High-fat feeding can reduce the number of activated neurons observed following the central administration of leptin in animals, but the effects on resistin are unknown. The present work compared the distribution of neurons in the brain that are activated by centrally administered resistin, or leptin alone, and, in combination, in rats fed a high fat (HFD) compared to a normal chow diet (ND). Immunohistochemistry for the protein, Fos, was used as a marker of activated neurons. The key findings are (i) following resistin or leptin, either alone or combined, in rats fed the HFD, there were no significant increases in the number of activated neurons in the paraventricular and arcuate nuclei, and in the lateral hypothalamic area (LHA). This contrasted with observations in rats fed a normal chow diet; (ii) in the OVLT and MnPO of HFD rats there were significantly less activated neurons compared to ND following the combined administration of resistin and leptin; (iii) In the PAG, RVMM, and NTS of HFD rats there were significantly less activated neurons compared to ND following resistin. The results suggest that the sensitivity to resistin in the brain was reduced in rats fed a HFD. This has similarities with leptin but there were instances where there was reduced sensitivity to resistin with no significant effects following leptin. This suggests diet influences neuronal effects of resistin.

Low-frequency membrane potential (Vm) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low-frequency Vm oscillations have been described in inactive awake animals, but it is unclear whether they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell Vm recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks. We recorded stereotyped 3–5 Hz Vm oscillations where the Vm baseline hyperpolarized as the Vm underwent high amplitude rhythmic fluctuations lasting 1–2 s in duration. When 3–5 Hz Vm oscillations coincided with visual cues, excitatory neuron responses to preferred cues were significantly reduced. Despite this disruption to sensory processing, visual cues were critical for evoking 3–5 Hz Vm oscillations when animals performed discrimination tasks and passively viewed drifting grating stimuli. Using pupillometry and animal locomotive speed as indicators of arousal, we found that 3–5 Hz oscillations were not restricted to unaroused states and that they occurred equally in aroused and unaroused states. Therefore, low-frequency Vm oscillations play a role in shaping sensory processing in visual cortical neurons, even during active wakefulness and decision making.

A long-standing objective in neuroscience has been to image distributed neuronal activity in freely behaving animals. Here we introduce NeuBtracker, a tracking microscope for simultaneous imaging of neuronal activity and behavior of freely swimming fluorescent reporter fish. We showcase the value of NeuBtracker for screening neurostimulants with respect to their combined neuronal and behavioral effects and for determining spontaneous and stimulus-induced spatiotemporal patterns of neuronal activation during naturalistic behavior.

Nitric oxide (NO) and carbon monoxide (CO) are important signaling molecules shaping vasomodulation. This paper reports simultaneous in vivo monitoring of NO, CO and dendritic summation of action potential at three different cortical regions: seizure focus and two additional places, vertically and horizontally separated by 1.2 mm from the seizure focus, during epileptic seizure induced by 4-aminopyrindine injection. An amperometric dual microsensor having a high spatiotemporal resolution monitored fast and dynamic changes of NO and CO, and neural changes were recorded with a glass pipet electrode for local field potential (LFP). At all three locations, onsets and offsets of NO and CO changes well synchronized with fast LFP changes, while the patterns and concentrations of NO and CO changes were varied depending on the sensing locations. The insertable NO/CO dual microsensor was successful to measure intimately linked NO and CO in acute seizure events with high sensitivity, selectivity, and spatiotemporal resolution.

Because of its role in drug-seeking, consumption and addictive behavior, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-induced memories. However, very few studies have focused on brain areas beyond the corticostriatal-limbic circuitry. Despite the growing evidence confirming the involvement of the cerebellum in drug-induced alterations, this structure has been traditionally disregarded in the addiction field (Miquel et al, 2009; Miquel et al, 2016). The general aim of the present research is to address wether the cerebellum is part of the neuronal systems that sustains the plasticity mechanisms underlying drug-induced conditioned memories. We have focused our research in an attempt to clarify if the cerebellum is involved in the acquisition and storage of drug memories. The present doctoral thesis contains three different chapters. In the first chapter, Involving the cerebellum in cocaine induced memory: pattern of cFos expression in mice trained to acquire conditioned preference for cocaine, we explored the pattern of neuronal activation as revealed by cFos immunoreactivity of mice trained to develop conditioned preference for an olfactory stimulus paired with cocaine. In the second one, entitled Cerebellar hallmarks of conditioned preference for cocaine, we used the same behavioral task of the first study in order to further extend the description of cFos expression patterns in cerebellar circuitry, including now the major inputs and one of the output nuclei of the cerebellum. In the last chapter, Cerebellar perineuronal nets in cocaine-induced Pavlovian memory: site does matter, we accomplished a broad analysis of perineuronal nets (PNNs) expression of cerebellar vermis. First, we analysed an outbred mouse strain trained to acquire preference for olfactory stimuli associated with cocaine. Second, α6Cre- Cacna1a mice (Galliano et al, 2013) were used to test if a reduction in the glutamate release of parallel fibres to Purkinje dendrites would alter the acquisition of cocainepreference conditioning and the expression of PNNs in the cerebellum., Debido a su papel en la búsqueda de drogas, el consumo y la conducta adictiva, hay un creciente interés en la identificación de los circuitos neuronales y mecanismos moleculares subyacentes en la formación, el mantenimiento y la recuperación de las memorias inducidas por drogas. Sin embargo, muy pocos estudios se han centrado en áreas cerebrales más allá de los circuitos corticoestriatal-límbicos. A pesar de la creciente evidencia que confirma la participación del cerebelo en las alteraciones inducidas por drogas, esta estructura ha sido tradicionalmente descartada en el campo de la adicción (Miquel et al, 2009; Miquel et al, 2016). El objetivo general de la presente investigación es abordar si el cerebelo forma parte de los sistemas neuronales que sostienen los mecanismos de plasticidad subyacentes a las memorias condicionadas inducidas por drogas. Hemos centrado nuestra investigación en un intento de aclarar si el cerebelo está involucrado en la adquisición y almacenamiento de memorias asociadas a drogas. La presente tesis doctoral contiene tres capítulos diferentes. En el primer capítulo: Involving the cerebellum in cocaine-induced memory: pattern of cFos expression in mice trained to acquire conditioned preference for cocaine, exploramos el patrón de activación neuronal revelado por inmunorreactividad de cFos en ratones entrenados para desarrollar preferencia condicionada por un estimulo olfatorio asociado a la cocaína. En el artículo, titulado Cerebellar hallmarks of conditioned preference for cocaine, se utilizó la misma tarea comportamental del primer estudio con el fin de ampliar la descripción del patrón deexpresión de cFos en la circuitrería cerebelar, incluyendo ahora los principales aferentes y uno de los núcleos de salida del cerebelo. En el último capítulo, Cerebellar perineuronal nets in cocaine-induced Pavlovian memory: site does matter, se realizó un amplio análisis de la expresión de PNNs en el vermis cerebeloso. En primer lugar, se realizó el análisis en ratones entrenados para adquirir preferencia por un estímulo olfatorio asociado con la cocaína. En segundo lugar, se utilizaron ratones modificados genéticamente de la cepa α6Cre-Cacna1a (Galliano et al, 2013) para probar si una reducción en la liberación de glutamato de las células granulares a las dendritas de Purkinje alteraría la adquisición de preferencia por estímulos asociados con la cocaína y la expresión de PNNs en el cerebelo.

Electroencephalography (EEG) can localize neural electrical activity and track in vivo brain functions in milliseconds with high temporal resolution. Even though EEG is said to be time accurate and spatial inaccurate, the approximate spatial information is still useful. In view of the shortcomings of imaging modalities, the purpose of our work is to propose EEG as a potential neurofeedback protocol since it can provide concurrent feedback and progressive states of neuronal activation. The preliminary work here intends to study the correspondence between the 2D EEG topography and brain images from fMRI for the normal adults during relaxation state and letter writing, being the first attempt ever reported. With OpenViBE as the platform, the EEG signal acquired was segmented, filtered and extracted for significant features, before the EEG topography is generated. Despite difficulty in finding the corresponding brain images, it is found that the EEG topography along the reading-writing pathway is a close match to images from fMRI studies and neurological theories.

Neuronal coherence is thought to constitute a unique substrate for information transmission distinct from firing rate. However, since the spatial scale of extracellular oscillations typically exceeds that of firing rates, it is unclear whether coherence complements or compromises the rate code. We examined responses in the macaque primary visual cortex and found that fluctuations in gamma-band (~40Hz) neuronal coherence correlated more with firing rate than oscillations in the local-field-potential (LFP). Although the spatial extent of LFP rhythms was broader, that of neuronal coherence was indistinguishable from firing rates. To identify the mechanism, we developed a statistical technique to isolate the rhythmic component of the spiking process and found that above results are explained by an activation-dependent increase in neuronal sensitivity to gamma-rhythmic input. Such adaptive changes in sensitivity to rhythmic inputs might constitute a fundamental homeostatic mechanism that prevents globally coherent inputs from undermining spatial resolution of the neural code.

Rats fed high fat diets have been shown to be impaired in hippocampal-dependent behavioral tasks, such as spatial recognition in the Y-maze and reference memory in the Morris water maze (MWM). It is clear from previous studies, however, that motivation and reward factor into the memory deficits associated with obesity and high-fat diet consumption, and that the prefrontal cortex and striatum and neurotransmitter dopamine play important roles in cognitive performance. In this series of studies we extend our research to investigate the effect of a high fat diet on striatal neurochemistry and performance in the delayed spatial win-shift radial arm maze task, a paradigm highly reliant on dopamine-rich brain regions, such as the striatum after high fat diet consumption. Memory performance, neuronal activation and brain dopaminergic levels were compared in rats fed a “Western” (21% fat, 0.15% cholesterol) chow diet compared to normal diet (6% fat, 0.15% cholesterol)-fed controls. Twelve weeks of dietary manipulation produced an increase in weight in western diet-fed rats, but did not affect learning and performance in the delayed spatial win-shift radial arm maze task. Concurrently, there was an observed decrease in dopamine levels in the striatum and a reduction of dopamine turnover in the hippocampus in western diet-fed rats. In a separate cohort of rats Fos levels were measured after rats had been placed in a novel arena and allowed to explore freely. In normal rats, this exposure to a unique environment did not affect neuronal activation. In contrast, rats fed a western diet were found to have significantly increased Fos expression in the striatum, but not prefrontal cortex or hippocampus. Our study demonstrates that while western diet consumption in rats produces weight gain and brain neuronal and neurotransmitter changes, it did not affect performance in the delayed spatial win-shift paradigm in the radial arm maze. We conclude that modeling the cognitive decline-obesity relationship is complex with considerations, of type of memory, behavioral task and dietary intervention (fat, fat and sugar, sugar, and cafeteria diets) all adding to our overall understanding.

This empirical single-participant fMRI case study partially replicates Belin, Zatorre, Lafaille, Ahad, and Pike (2000) research on voice-selective areas in the auditory cortex. It hypothesises that brain areas, sensitive to human vocal sounds, show greater neural activation than non-human ones. A 1X3 ANOVA design was used in this study contrasted by two conditions: sound vs. silence and voice vs. non-voice. The findings supported the hypothesis, noting also possible individual differences to the degree of voice activation in both hemispheres. Suggestions for a future replication could discuss voice/non-voice and speech/non-speech neuronal activation in the brain, auditory and visual neural responsiveness to voice and face modalities, and evolutionary assumptions in regard to sound- and voice-selective reactivity.

Yawning is often observed not only in a state of boredom or drowsiness but also in stressful emotional situations, suggesting that yawning is an emotional behavior. However, the neural mechanisms for yawning during stressful emotional situations have not been fully determined, though previous studies have suggested that both parvocellular oxytocin (OT) and corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) are responsible for induction of yawning. Thus, using ethological observations and c-Fos immunohistochemistry, we examined whether emotional stress evoked by classical fear conditioning is involved in induction of yawning behavior in freely moving rats. Emotional stress induced yawning behavior that was accompanied by anxiety-related behavior, and caused neuronal activation of the central nucleus of the amygdala (CeA), as well as increases in activity of both OT and CRF neurons in the PVN. These results suggest that emotional stress may induce yawning behavior, in which the neuronal activation of the CeA may have a key role.

Functional connectivity can be defined as the statistically temporal dependency of neuronal activation patterns of anatomically separated brain regions. The analysis of functional connectivity can lead to brain networks. Here, we report the result of an experiment that has shown two different brain networks related with the appreciation of beauty, corresponding to different time spans in the cognitive processes implied. We describe and discuss such networks, as well as their eventual evolutionary meaning. © 2014 Accademia Nazionale dei Lincei.

In mammals, the cerebral cortex microvasculature (CCM) of the neopallium plays important roles in the physiological and pathological processes of the brain. The aim of the present work is to analyze the CCM by use of the SEM-vascular corrosion cast technique, and to examine the immunocytochemical characteristics of the CCM in adult domestic ruminants (cattle, buffalo, and sheep) by using the SEM-immunogold technique. The CCM originated from the very small, finger-like terminal branches of the macrovasculature of the brain. The superficial cortical arterioles were more numerous than the deep straight arterioles which proceeded toward the white matter. The surface casts of the arterioles and capillaries of the cerebral cortex showed ring-shaped formations in the arterioles and at the origin of the capillaries. All capillaries down-stream from these ring-shaped formations were flaccid. Casts of the capillaries showed wrinkles due to the presence of endothelial folds, which is characteristic of varying blood pressure. Formations having intense anti-GIFAP immunoreactivity were frequently evident along the course of the blood capillaries in the cerebral cortex. These formations were probably astrocytes that might regulate the cerebral microcirculation based on physiological and pathological stimuli, such as neuronal activation. Microsc. Res. Tech. 77:257–263, 2014. © 2014 Wiley Periodicals, Inc.

According to the “two streams” hypothesis, the lateral entorhinal (LEC) and the perirhinal (PrC) cortices process information related to items (a “what” stream), the postrhinal (POR) and the medial entorhinal cortices (MEC) process spatial information (a “where” stream), and both types of information are integrated in the hippocampus (HIP). However, within the framework of memory function, only the HIP is reliably shown to preferentially process spatial information, and the PrC items' features. In contrast, the role of the LEC and MEC in memory is virtually unexplored, and conflicting results emerge for the POR. Moreover, the specific contribution of the hippocampal subfields CA1 and CA3 to spatial and non-spatial memory is not thoroughly understood. To investigate which of these areas is specifically tuned to spatial demands or stimulus identity (odor or object), we assessed the pattern of activation of these areas during recognition memory by detecting the immediate-early gene Arc, commonly used as a marker of neuronal activation. We report that all MTL areas were recruited during the spatial and the non-spatial tasks. However, the LEC, MEC, POR, and CA1 were activated to a comparable level in spatial and non-spatial tasks, while the PrC was tuned to stimulus-type, not spatial demands, and CA3 to spatial demands but not stimulus-type. Results are discussed within the frame of a recent model suggesting that the MTL could be segregated in terms of memory processes, such as recollection and familiarity, rather than information content. © 2013 Wiley Periodicals, Inc.

The vasculature in the brain is an actively regulated organ which, on the one hand, is influenced by global changes of systemic parameters (systemic blood pressure, blood gases, and blood pH) and, on the other hand, is capable of locally directing the blood to the regions of demand with high spatial and temporal resolution. Together with pericytes and astrocytes, as part of the neurovascular unit, cerebral vascular endothelium forms the tight blood-brain barrier and has an important immuno-regulatory function. Within this book chapter the main principles of the vascular architecture and the cellular components at the neurovascular unit forming the blood-brain barrier will be described before summarizing the main mechanisms of global blood flow regulation to changes in systemic parameters as well as giving an overview on the local regulation according to the cellular demand during neuronal activation.

Amphibians are central to discussions of vertebrate evolutionbecause they represent the transition from aquatic toterrestrial life, a transition with profound consequences forthe selective pressures shaping brain evolution. Spatial navigationis one class of behavior that has attracted the interestof comparative neurobiologists because of the relevance ofthe medial pallium/hippocampus, yet, surprisingly, in this regardamphibians have been sparsely investigated. In the currentstudy, we trained toads to locate a water goal relying onthe boundary geometry of a test environment (GeometryOnly)or boundary geometry coupled with a prominent, visualfeature cue (Geometry-Feature). Once learning hadbeen achieved, the animals were given one last training sessionand their telencephali were processed for c-Fos activation.Compared to control toads exposed to the test environmentfor the first time, geometry-only toads were found to have increased neuronal labeling in the medial pallium, thepresumptive hippocampal homologue, while geometry-featuretoads were found to have increased neuronal labelingin the medial, dorsal, and lateral pallia. The data indicate medialpallial participation in guiding navigation by environmentalgeometry and lateral, and to a lesser extent dorsal,pallial participation in guiding navigation by a prominent visualfeature. As such, participation of the medial pallium/hippocampus in spatial cognition appears to be a conservedfeature of terrestrial vertebrates even if their life history is stilltied to water, a brain-behavior feature seemingly at least asancient as the evolutionary transition to life on land. Fil: Sotelo, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; Argentina Fil: Daneri, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; Argentina Fil: Bingman, Verner Peter. Bowling Green State University; Estados Unidos Fil: Muzio, Ruben Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; Argentina

We previously reported that neurogenic hypertension is associated with a reduction of Angiotensin Converting Enzyme 2 (ACE2) activity and an increase in A Disintegrin And Metalloprotease 17 (ADAM17) activity in the hypothalamus. Since ADAM17 is known to be expressed in multiple cell types and can be activated by various receptors, we tested the hypothesis that neuronal AT1a receptors (AT1aR) are necessary for ADAM17-mediated ACE2 shedding during neurogenic hypertension. DOCA-salt treatment (DOCA 1mg/g body weight sc + 1% saline p.o./3 weeks) was given to male neuronal AT1aR knockdown mice (AT1aR floxed crossed with Nefh-cre mice, 14-16 week-old) and their non-transgenic (NT) littermates (n=8/group). Following DOCA-salt treatment, enzyme activity assays were performed in hypothalamus of both DOCA-salt-treated and sham mice. Unlike in NT mice, ADAM17 activity was not increased by DOCA-salt treatment in the hypothalamus of neuronal AT1aR knockdown mice (153.7 ±23.8 vs. 128.5 ±11.6 FU/min, P =0.22). To assess whether impaired ADAM17 activation resulted from down-regulation of neuronal AT1aR, or was due to an attenuated BP rise, wild-type mice were infused with norepinephrine (NE; 4 ug/kg/min/14 d, n=6/group). Contrary to DOCA-salt hypertension, ACE2 activity in the hypothalamus remained intact during NE-induced hypertension and there was no significant increase in ADAM17 activity (59.1 ±4.3 vs. 52.3 ±11.7 FU/min, P =0.29). Using FACS, neurons, astrocytes and non-neuronal/non-astrocyte cells were sorted from the hypothalamus. A significant increase in ADAM17 mRNA resulting from DOCA-salt treatment (+1.72 ±0.19 fold vs. sham, P Taken together, our data provide strong evidence that activation of neuronal AT1aR is responsible for ADAM17-mediated ACE2 shedding and the maintenance of neurogenic hypertension.