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International audience; Les addictions comportementales incluent l’addiction aux jeux de hasard et d’argent ou jeu pathologique, addiction aux jeux vidéo, achats compulsifs, addictions alimentaires, dépendance à l’activité physique, dépendances sexuelles et affectives, etc. Il existe des similitudes neurobiologiques, psychopathologiques et comportementales entre les addictions avec produit et les addictions comportementales. Le but de cette revue est d’illustrer de façon simple les changements cérébraux que nous avons observés dans le jeu pathologique grâce à la neuro-imagerie (IRM fonctionnelle) lors d’expériences sollicitant le système de récompense ou des biais cognitifs. Les résultats permettent de mieux comprendre l’engagement des régions cérébrales et les mécanismes mis en jeu lors du traitement de récompenses et de décisions inadaptées dans le jeu pathologique.

Brain-derived neurotrophic factor (BDNF) plays a central pivotal role in the development of the cardiovascular system. Recent evidence suggests that BDNF has adverse subclinical cardiac remodeling in participants with cardiovascular disease risk factors. Relating serum BDNF levels with two-dimensional echocardiographic indices will provide insights into the BDNF mediated pathophysiology in coronary artery disease (CAD) that may shed light upon potential diagnostic biomarkers. For the study, 221 participants were recruited and classified based on coronary angiogram examination as control (n = 105) and CAD (n = 116). All participants underwent routine blood investigation, two-dimensional echocardiography, and serum BDNF estimation. As a result, total cholesterol, triglyceride, low-density lipid, high-density lipid, HbA1c (glycosylated hemoglobin), serum creatinine, eosinophils, lymphocyte, monocytes, neutrophils, and platelets were significantly elevated in CAD individuals compared to controls. Notably, the serum BDNF was significantly lower in individuals with CAD (30.69 ± 5.45 ng/ml) than controls (46.58 ± 7.95 ng/ml). Multivariate regression analysis showed neutrophils, total cholesterol, left ventricular mass index, mitral inflow E/A ratio, and pulmonary vein AR duration were associated with low BDNF in CAD. Four independent support vector machine (SVM) models performed to ensure the BDNF level in the classification of CAD from healthy controls. Particularly, the model with serum BDNF concentration and blood parameters of CAD achieved significant improvement from 90.95 to 98.19% in detecting CAD from healthy controls. Overall, our analysis provides a significant molecular linkage between the serum BDNF level and cardiovascular function. Our results contribute to the emerging evidence of BDNF as a potential diagnostic value in CAD that might lead to clinical application.

44th Congress of the Société de Biomécanique, Poitiers, FRANCE, 28-/10/2019 - 30/10/2019; The mechanical phenomena which occur in the subarachnoid space have been studied either from a structural point of view particularly focusing on the spinal cord (SC) or from a fluid point of view focusing on the cerebrospinal fluid (CSF) flow. Fluid-structure interaction (FSI) approaches provide new perspectives to numerically describe the physiological phenomenon. It has been showed that the CSF acts in a passively way on the central nervous system as shock absorber in compressive spinal cord injuries (Fradet et al. 2016). However, we are not aware of any study that provide stress values induced by the active physiological role of the pulsatile CSF flow profile on the spinal cord in 3D. The purpose of this study is to quantify the maximum Von Mises stress generated in the spinal cord induced by an healthy pulsatile flow profile of the CSF.

44th Congress of the Société de Biomécanique, Poitiers, FRANCE, 28-/10/2019 - 30/10/2019; Recent news in Rugby Union highlight the necessity to prevent concussions and injuries during training and matches. The number of concussions has indeed been reported to increase in the last decades (Finch et al. 2013). This is mostly due to the anatomy of professional rugby players (muscular development, higher body mass index- BMI).While the rugby union rules have been changing to promote safer practice in scrum, the players get highly injured during tackles (Fuller et al. 2010). Multiple influences on injury risks, such as the impact conditions or the player's morphology, have not been fully studied. In tackling, both the tackler (T) and the ball carrier (BC), their morphology and initial position need to be studied to fully describe the tackle impacts. Experimentally, on field data can be acquired with sensors and epidemiological studies have been carried to correlate the type of injury with the impact conditions (Kuster et al. 2012)

A recent hypothesis purports that spinal manipulation may cause changes at a brain level. Functional Neurology, a mainly chiropractic approach, promotes the use of spinal manipulation to improve 'brain function' as if it were a proven construct. No systematic review has been performed to investigate how well founded this hypothesis is.To investigate whether spinal manipulation has an effect on 'brain function' that is associated with any clinical benefits.In this systematic review, the literature was searched in PubMed, Embase, and PEDro (final search February 2018). We included randomized or non-randomized controlled studies, in which spinal manipulation was performed to any region of the spine, applied on either symptomatic or asymptomatic humans, and compared to a sham or to another type of control. The outcome measures had to be stated as direct or proxy markers of 'brain function'. Articles were reviewed blindly by at least two reviewers, using a quality checklist designed for the specific needs of the review. Studies were classified as of 'acceptable', 'medium', or 'low' methodological quality. Results were reported in relation to (i) control intervention (sham, 'inactive control', or 'another physical stimulus') and (ii) study subjects (healthy, symptomatic, or with spinal pain" subjects/spinal pain"), taking into account the quality. Only results obtained from between-group or between-intervention comparisons were considered in the final analysis.Eighteen of 1514 articles were included. Studies were generally of 'low' or 'medium' methodological quality, most comparing spinal manipulation to a control other than a sham. Thirteen out of the 18 studies could be included in the final analysis. Transitory effects of different types of 'brain function' were reported in the three studies comparing spinal manipulation to sham (but of uncertain credibility), in "subclinical neck/spinal pain" subjects or in symptomatic subjects. None of these three studies, of 'medium' or 'acceptable' quality, investigated whether the neurophysiological effects reported were associated with clinical benefits. The remaining 10 studies, generally of 'low' or 'medium' quality, compared spinal manipulation to 'inactive control' or 'another physical stimulus' and similarly reported significant between-group differences but inconsistently.The available evidence suggests that changes occur in 'brain function' in response to spinal manipulation but are inconsistent across and - sometimes - within studies. The clinical relevance of these changes is unknown. It is therefore premature to promote the use of spinal manipulation as a treatment to improve 'brain function'.Une hypothèse récente propose que la manipulation vertébrale causerait des changements neurophysiologiques au niveau du cerveau. En Neurologie Fonctionnelle, approche principalement présente en chiropraxie, l’utilisation de la manipulation vertébrale est déjà promue comme capable d’améliorer le fonctionnement du cerveau. A ce jour, aucune revue systématique de la littérature n’a été conduite afin de connaître l’étendue et la qualité de l’évidence scientifique susceptible de justifier cet usage de la manipulation vertébrale.Déterminer, à travers une revue systématique et critique de la littérature, si la manipulation vertébrale a un effet (spécifique) sur le cerveau et, si oui, si celui-ci est associé à un effet clinique.Le moteur de recherche PubMed et deux bases de données, Embase et PEDro, ont fait l’objet d’une recherche bibliographique (actualisée en février 2018). Les critères d’inclusion étaient: essais contrôlés, randomisés ou non, dans lesquels la manipulation vertébrale avait été comparée à un placébo ou à un autre type de contrôle, chez des sujets symptomatiques ou asymptomatiques. La manipulation vertébrale pouvait avoir été effectuée au niveau de n’importe quelle région de la colonne vertébrale et les critères de jugement utilisés devaient être indiqués comme capables de mesurer, directement ou indirectement, une forme ‘d’activité cérébrale’. La qualité méthodologique des études a été évaluée de manière indépendante par au moins deux chercheurs à l’aide d’une grille de qualité créée pour les besoins de cette revue. Les études ont été classifiées comme étant de qualité méthodologique ‘acceptable’, ‘moyenne’, ou ‘faible’. Les résultats ont été rapportés de façon narrative, en fonction du type de contrôle utilisé (placébo, ‘inactif’, ou ‘autre stimulus physique’) et du type de sujets d’étude (sans problème de santé, symptomatiques, ou présentant des « douleurs rachidiennes subcliniques »), en tenant compte de la qualité méthodologique. Seuls les résultats issus de comparaisons inter-groupes ont été pris en compte dans notre analyse finale.Dix-huit articles parmi les 1514 titres obtenus ont été inclus. Les études étaient pour la plupart de qualité méthodologique ‘faible’ ou ‘moyenne’ et avaient principalement comparé la manipulation vertébrale à une intervention autre que placébo. Les résultats rapportés dans 13 des 18 articles inclus ont finalement été pris en compte. Un effet transitoire sur différentes formes ‘d’activité cérébrale’ a été rapporté à l’issue de trois études dans lesquelles la manipulation vertébrale avait été comparée à un placébo (de crédibilité cependant incertaine), chez des sujets présentant des « douleurs rachidiennes subcliniques » (La littérature scientifique suggère que des changements neurophysiologiques surviennent au niveau du cerveau en réponse à la manipulation vertébrale mais, de façon inconsistante. La pertinence clinique de ces changements n’est pas connue. Ainsi, il est prématuré d’attribuer à la manipulation vertébrale des bénéfices cliniques via un effet sur le cerveau.

The periaqueductal gray (PAG) is a mesencephalic brain structure involved in the expression of numerous behaviours such as maternal, sexual and emotional. Histological approaches showed the PAG is composed by subdivisions with specific cell organisation, neurochemical composition and connections with the rest of the brain. The comparison of studies performed in rodents and cats as the most often examined species, suggests that PAG organisation differs between mammals. However, we should also consider the plurality of the methods used in these studies that makes difficult the comparison of the PAG organisation between species. Therefore, to study the PAG in all mammals including human, the most relevant in vivo imaging method seems to be the magnetic resonance imaging (MRI). The purpose of this review was to summarize the knowledge of the anatomical organisation of the PAG in mammals and highlights the benefits of MRI methods to extend this knowledge. Results obtained by MRI so far support the conclusions of ex vivo studies, especially to describe the subdivisions and the connections of the PAG. In these latter, diffusion-weighted MRI and functional connectivity seem the most appropriate methods. In conclusion firstly, the MRI seems to be the best judicious method to compare species and improve the comprehension of the role of the PAG. Secondly, MRI is an in vivo method aimed to manage repeated measures in the same cohort of subjects allowing to study the impact of aging and the development on the anatomical organisation of the PAG.

Individual creativity, defined as the ability to achieve a production that is both original and appropriate, results in part from mental operations that may be related to the functioning of the brain. The challenge in this field of research is to understand what these operations are, and what cerebral networks underlie them. Although these questions are not fully elucidated, advances in the neuroscience of creativity have identified different brain networks that support distinct mechanisms of creativity. Recent data from cognitive and functional neuroimaging studies indicate that creativity is based on the interaction between associative thinking likely underpinned by the default mode network and cognitive control processes supported by control-related networks, including fronto-parietal networks. The study of brain-damaged patients made it possible to test this model and to establish a more causal link between the creative processes and these brain networks. The lesion approach has indeed shown the critical role of the default mode network and the left frontoparietal control network in the associative and control processes, respectively, and has identified crucial nodes in these networks. The few lesion studies carried out also suggest functional specialization of the prefrontal cortex for distinct creative processes. In this review, we integrate the results of lesion studies and noninvasive brain stimulation studies with the findings of recent functional imaging studies in healthy subjects to clarify our understanding of the brain mechanisms of creativity., La créativité d’un individu, définie comme la capacité à réaliser une production à la fois originale et appropriée, résulte en partie d’opérations mentales pouvant être reliées au fonctionnement du cerveau. L’enjeu dans ce champ de recherche est de comprendre quelles sont ces opérations, et quels réseaux cérébraux les sous-tendent. Bien que ces questions ne soient pas entièrement élucidées, des avancées des neurosciences de la créativité ont permis d’identifier différents réseaux cérébraux supportant des mécanismes distincts de créativité. Les données récentes des études cognitives et de neuro-imagerie fonctionnelle indiquent que la créativité repose sur l’interaction entre la pensée associative, probablement sous-tendue par le réseau de mode par défaut, et les processus de contrôle cognitif supportés par des réseaux de contrôle, incluant un réseau fronto-pariétal. L’étude de patients cérébro-lésés a permis de tester ce modèle et d’établir un lien plus causal entre les processus créatifs et ces réseaux cérébraux. L’approche lésionnelle a en effet montré le rôle critique du réseau de mode par défaut et du réseau de contrôle fronto-pariétal gauche dans les processus associatifs et de contrôle, respectivement, et d’identifier les nœuds essentiels de ces réseaux. Les quelques études lésionnelles réalisées suggèrent également une spécialisation fonctionnelle du cortex préfrontal pour des processus créatifs distincts. Dans la présente revue, nous intégrons les résultats des études lésionnelles et de stimulation cérébrale non invasive aux conclusions d’études récente d’imagerie fonctionnelle afin de clarifier nos connaissances sur les bases cérébrales de la créativité.

International audience; Sex-biased gene expression is the mode through which sex dimorphism arises from a nearly identical genome, especially in organisms without genetic sex determination. Teleost fishes show great variations in the way the sex phenotype forms. Among them, Sparidae, that might be considered as a model family displays a remarkable diversity of reproductive modes. In this study, we sequenced and analyzed the sex-biased transcriptome in gonads and brain (the tissues with the most profound role in sexual development and reproduction) of two sparids with different reproductive modes: the gonochoristic common dentex, Dentex dentex, and the protandrous hermaphrodite gilthead seabream, Sparus aurata. Through comparative analysis with other protogynous and rudimentary protandrous sparid transcriptomes already available, we put forward common male and female-specific genes and pathways that are probably implicated in sex-maintenance in this fish family. Our results contribute to the understanding of the complex processes behind the establishment of the functional sex, especially in hermaphrodite species and set the groundwork for future experiments by providing a gene toolkit that can improve efforts to control phenotypic sex in finfish in the ever-increasingly important field of aquaculture.

Background Although the overall brain organization is shared in vertebrates, there are significant differences within subregions among different groups, notably between Sarcopterygii (lobe-finned fish) and Actinopterygii (ray-finned fish). Recent comparative studies focusing on the ventricular morphology have revealed a large diversity of the hypothalamus. Here, we study the development of the inferior lobe (IL), a prominent structure forming a bump on the ventral surface of the teleost brain. Based on its position, IL has been thought to be part of the hypothalamus (therefore forebrain). Results Taking advantage of genetic lineage-tracing techniques in zebrafish, we reveal that cells originating from her5-expressing progenitors in the midbrain-hindbrain boundary (MHB) participate in the formation of a large part of the IL. 3D visualization demonstrated how IL develops in relation to the ventricular system. We found that IL is constituted by two developmental components: the periventricular zone of hypothalamic origin and the external zone of mesencephalic origin. The mesencephalic external zone grows progressively until adulthood by adding new cells throughout development. Conclusion Our results disprove a homology between the IL and the mammalian lateral hypothalamus. We suggest that the IL is likely to be involved in multimodal sensory integration rather than feeding motivation. The teleost brain is not a simpler version of the mammalian brain, and our study highlights the evolutionary plasticity of the brain which gives rise to novel structures. Electronic supplementary material The online version of this article (10.1186/s12915-019-0631-y) contains supplementary material, which is available to authorized users.

International audience; Primates, like all animals live in an environment that includes others. They can be detected by others and can influence the likelihood (and consequences) of this detection by sending signals. Signals are bodily features or behaviors of the signaler that trigger specific behaviors in the receiver. The receiver, signaler, signal and medium are the four basic building blocks of any communication cycle. Each component can be considered separately, but in the service of communication they are interdependent and defined only in relation to one other. Cycles of reciprocal signal exchange mediate social interactions, but even “asocial” species coordinate reproduction, manage conflict over territory, and may anticipate and influence potential predators and prey. Communication arose long before the evolution of primates, animals and even neurons, yet is a crucial aspect of primate behavior and of their nervous system evolution. In this review, we examine how exchanges take place among primates and how neural systems act to mediate them.; Les primates, comme tous les animaux, vivent dans un environnement qui comprend d'autres individus. Ils peuvent être détectés par ceux-ci et influencer la probabilité (et les conséquences) de cette détection en envoyant des signaux. Les signaux sont des caractéristiques corporelles transitoires ou des comportements produits par l’émetteur qui déclenchent des comportements spécifiques chez le récepteur. Le récepteur, l’émetteur, le signal (ou message) et les signes qui constituent le message sont les quatre éléments de base du cycle de communication. Chaque composant peut être considéré séparément, mais au service de la communication, ils sont interdépendants et définis uniquement les uns par rapport aux autres. Les échanges de signaux interviennent pendant les interactions sociales, mais même les espèces « non-sociales » coordonnent leur reproduction, gèrent les conflits sur leur territoire et peuvent anticiper et influencer les prédateurs et les proies potentiels. La communication est apparue bien avant l'évolution des primates, des animaux et même des neurones, mais constitue un aspect crucial du comportement des primates et de l'évolution de leur système nerveux. Dans cette revue, nous examinons comment les primates communiquent entre eux et comment les systèmes neuronaux sous-tendent ces échanges.

International audience; General anesthesia (GA) is a reversible manipulation of consciousness whose mechanism is mysterious at the level of neural networks leaving space for several competing hypotheses. We recorded electrocorticography (ECoG) signals in patients who underwent intracranial monitoring during awake surgery for the treatment of cerebral tumors in functional areas of the brain. Therefore, we recorded the transition from unconsciousness to consciousness directly on the brain surface. Using frequency resolved interferometry; we studied the intermediate ECoG frequencies (4–40 Hz). In the theoretical study, we used a computational Jansen and Rit neuron model to simulate recovery of consciousness (ROC). During ROC, we found that f increased by a factor equal to 1.62 ± 0.09, and δf varied by the same factor (1.61 ± 0.09) suggesting the existence of a scaling factor. We accelerated the time course of an unconscious EEG trace by an approximate factor 1.6 and we showed that the resulting EEG trace match the conscious state. Using the theoretical model, we successfully reproduced this behavior. We show that the recovery of consciousness corresponds to a transition in the frequency (f, δf) space, which is exactly reproduced by a simple time rescaling. These findings may perhaps be applied to other altered consciousness states. General anesthesia (GA) is an example of a reversible manipulation of consciousness, which is performed every day in hospitals around the world. While the mechanisms that underlie the effects of anesthetics become clearer at the cellular level 1,2 , the effects of anesthetics on brain activity at the scale of functional neural networks are still debated, which leaves space for several competing hypotheses 3. GA shares many common pathways with sleep, specifically with respect to the loss and recovery of consciousness, but it also displays specific electrophysiological features that are related to drug effects. The changes in the EEG during sleep or anesthesia are empirically well described but their function and generation are still unknown 4. The loss of consciousness induced by the widely used anaesthetic propofol is associated with an increase of power in the low-frequencies of the EEG and the emergence of strong and highly structured rhythmic activities in the EEG 5–7 corresponding to frontal alpha oscillations (8 to 13 Hz) 5. Many anesthetics share the same effects 8. Moreover, for some authors, the characteristic changes in the EEG during GA are similar to those observed in the first stages of sleep 9,10. A consistent explanation for these findings is missing and the behavior is still debated, which has led to different models 3,11–14. In this article, we recorded Electrocorticography (ECOG) after stopping the infusion of anaesthetics for brain surgery requiring functional testing in awake patients. We investigated the reorganization of dynamics in local

The many functions of astrocytes, such as glutamate recycling and morphological plasticity, enable them to stabilize synapses environment and protect neurons. Little is known about how they adapt to glucocorticoid-induced stress, and even less about the influence of dietary factors. We previously showed that omega-3 polyunsaturated fatty acids (ω3PUFA), dietary fats which alleviate stress responses, influence the way astroglia regulate glutamatergic synapses. We have explored the role of docosahexaenoic acid (DHA), the main ω3PUFA, in the astroglial responses to corticosterone, the main stress hormone in rodents to determine whether ω3PUFA help astrocytes resist stress. Cultured rat astrocytes were enriched in DHA or arachidonic acid (AA, the main ω6PUFA) and given 100 nM corticosterone for several days. Corticosterone stimulated astrocyte glutamate recycling by increasing glutamate uptake and glutamine synthetase (GS), and altered the astrocyte cytoskeleton. DHA-enriched astrocytes no longer responded to the action of corticosterone on glutamate uptake, had decreased GS, and the cytoskeletal effect of corticosterone was delayed, while AA-enriched cells were unaffected. The DHA-dependent anti-corticosterone effect was related to fewer glucocorticoid receptors, while corticosterone increased DHA incorporation into astrocyte membranes. Thus, DHA helps astrocytes resist the influence of corticosterone, so perhaps promoting a sustainable response by the stressed brain. We show that corticosterone increases the glutamate recycling capacity of rat cortical astrocytes in culture, and alters their morphology, which may be detrimental in the long term. Increasing the membrane incorporation of docosahexaenoic acid (DHA), the main omega-3 in brain, reduces the amount of glucocorticoid receptors (GR) and prevents the effects of corticosterone. This may help the astrocytes maintain a functional phenotype in chronic stress situations.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain–behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies., Highlights • We review the neural vulnerability factors related to obesity and eating disorders. • We compare the pros and cons of neuroimaging techniques to study eating behavior. • We present non-invasive strategies to modulate food-related brain processes. • We also present invasive neuromodulation methods such as VNS and DBS. • We discuss about neuroimaging and neuromodulation for prevention and therapy.

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that 13C nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing 13C nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo. Shishmarev et al. use rapid dissolution dynamic nuclear polarization to monitor glyoxalase activity in a non-invasive manner using nuclear magnetic resonance spectroscopy. They apply their method to monitor and quantify metabolism of methylglyoxal in human red blood cells and mouse tissues.

Nuclear receptors (NR) are emerging as key players in the central nervous system (CNS) with reported implications in physiological and pathophysiological conditions. While other NR have been studied, it is unknown whether invalidation of the pregnane xenobiotic receptor (PXR, NR1I2) corresponds to neurological modifications in the adult brain. PXR-/- C57BL/6j and wild type mice were used to investigate: i) recognition memory, motor coordination, and anxiety-like behaviors; ii) longitudinal video-electroencephalographic (EEG) recordings and frequency wave analysis; iii) neurovascular structures by histological evaluation and expression of the cerebrovascular tight junctions ZO1 and CLDN5. Absence of PXR was associated with anxiety-like behavior and recognition memory impairment in adult mice. The latter was simultaneous to an electroencephalographic signature of lower theta frequency during sleep and abnormal delta waves. Neurophysiological changes did not correspond to significant structural changes in the adult brain, expect for a localized and minor increase in the fronto-parietal neurovascular density and reduced ZO1, but not CLDN5, expression in isolated brain capillaries. Our results converge with existing evidence supporting a link between NR expression and brain physiology. Although the exact modalities remain to be elucidated, the possibility that extra-physiological modulation of PXR may constitute a pathophysiological entry point or a molecular target for brain diseases is proposed.

The characterization of brain tissue is crucial to better understand neurological disorders. Mechanical characterization is an emerging tool in that field. The purpose of this work was to validate a transient ultrasound technique aimed at measuring dispersion of mechanical parameters of the brain tissue. The first part of this work was dedicated to the validation of that technique by comparing it with two proven rheology methods: a rotating plate rheometer, and a viscoelastic spectroscopy apparatus. Experiments were done on tissue mimicking gels. Results were compared on storage and loss modulus in the 20-100 Hz band. Our method was validated for the measurement of storage modulus dispersion, with some reserves on the measurement of loss modulus. The second part of this work was the measurement of the mechanical characteristics of ex vivo human white matter. We were able to measure the dispersion of the storage and loss modulus in the 20-100 Hz band, fitting the data with a custom power law model.

A newly proposed form of brain structural plasticity consists of non-newly generated, “immature” neurons of the adult cerebral cortex. Similar to newly generated neurons, these cells express the cytoskeletal protein Doublecortin (DCX), yet they are generated prenatally and then remain in a state of immaturity for long periods. In rodents, the immature neurons are restricted to the paleocortex, whereas in other mammals, they are also found in neocortex. Here, we analyzed the DCX-expressing cells in the whole sheep brain of both sexes to search for an indicator of structural plasticity at a cellular level in a relatively large-brained, long-living mammal. Brains from adult and newborn sheep (injected with BrdU and analyzed at different survival times) were processed for DCX, cell proliferation markers (Ki-67, BrdU), pallial/subpallial developmental origin (Tbr1,Sp8), and neuronal/glial antigens for phenotype characterization. We found immature-like neurons in the whole sheep cortex and in large populations of DCX-expressing cells within the external capsule and the surrounding gray matter (claustrum and amygdala). BrdU and Ki-67 detection at neonatal and adult ages showed that all of these DCX+cells were generated during embryogenesis, not after birth. These results show that the adult sheep, unlike rodents, is largely endowed with non-newly generated neurons retaining immature features, suggesting that such plasticity might be particularly important in large-brained, long-living mammals.SIGNIFICANCE STATEMENTBrain plasticity is important in adaptation and brain repair. Structural changes span from synaptic plasticity to adult neurogenesis, the latter being highly reduced in large-brained, long-living mammals (e.g., humans). The cerebral cortex contains “immature” neurons, which are generated prenatally and then remain in an undifferentiated state for long periods, being detectable with markers of immaturity. We studied the distribution and developmental origin of these cells in the whole brain of sheep, relatively large-brained, long-living mammals. In addition to the expected cortical location, we also found populations of non-newly generated neurons in several subcortical regions (external capsule, claustrum, and amygdala). These results suggests that non-neurogenic, parenchymal structural plasticity might be more important in large mammals with respect to adult neurogenesis.

International audience; During mammalian embryonic development, GnRH neurones differentiate from the nasal placode and migrate through the nasal septum towards the forebrain. We previously showed that a category of glial cells, the olfactory ensheathing cells (OEC), forms the microenvironment of migrating GnRH neurones. Here, to characterize the quantitative and qualitative importance of this glial, we investigated the spatiotemporal maturation of glial cells in situ and the role of maturing glia in GnRH neurones development ex vivo. More than 90% of migrating GnRH neurones were found to be associated with glial cells. There was no change in the cellular microenvironment of GnRH neurones in the regions crossed during embryonic development as glial cells formed the main microenvironment of these neurones (53.4%). However, the phenotype of OEC associated with GnRH neurones changed across regions. The OEC progenitors immunoreactive to brain lipid binding protein formed the microenvironment of migrating GnRH neurones from the vomeronasal organ to the telencephalon and were also present in the diencephalon. However, during GnRH neurone migration, maturation of OEC to [GFAP+] state (glial fibrillary acid protein) was only observed in the nasal septum. Inducing depletion of OEC in maturation, using transgenic mice expressing herpes simplex virus thymidine kinase driven by the GFAP promoter, had no impact on neurogenesis or on triggering GnRH neurones migration in nasal explant culture. Nevertheless, depletion of [GFAP+] cells decreased GnRH neurites outgrowth by 57.4%. This study suggests that specific maturation of OEC in the nasal septum plays a role in morphological differentiation of GnRH neurones.

International audience; The adult brain contains niches of neural stem cells that continuously add new neurons to selected circuits throughout life. Two niches have been extensively studied in various mammalian species including humans, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus. Recently, studies conducted mainly in rodents have identified a third neurogenic niche in the adult hypothalamus. In order to evaluate whether a neural stem cell niche also exists in the adult hypothalamus in humans, we performed multiple immunofluorescence labeling to assess the expression of a panel of neural stem/progenitor cell (NPC) markers (Sox2, nestin, vimentin, GLAST, GFAP) in the human hypothalamus and compared them with the mouse, rat and a non-human primate species, the grey mouse lemur (Microcebus murinus). Our results show that the adult human hypothalamus contains four distinct populations of cells that express the five NPC markers: i) a ribbon of small stellate cells that lines the third ventricular wall behind a hypocellular gap, similar to that found along the lateral ventricles, ii) ependymal cells, iii) tanycytes, which line the floor of the third ventricle in the tuberal region, and iv) a population of small stellate cells in the suprachiasmatic nucleus. In the mouse, rat and mouse lemur hypothalamus, co-expression of NPC markers is primarily restricted to tanycytes, and these species lack a ventricular ribbon. Our work thus identifies four cell populations with the antigenic profile of NPCs in the adult human hypothalamus, of which three appear specific to humans.

IF 3.566; International audience; The polysialic acid (PSA) is a large glycan that is added to cell-surface proteins during their post-translational maturation. In the brain, PSA modulates distances between cells and controls the plasticity of the nervous system. In the hypothalamus, PSA is involved in many aspects of energy balance including food intake, osmoregulation, circadian rhythm, and sleep. In this work, we investigated the role of hypothalamic PSA in the regulation of plasma cholesterol levels and distribution. We report that HFD consumption in mice rapidly increased plasma cholesterol, including VLDL, LDL, and HDL-cholesterol. Although plasma VLDL-cholesterol was normalized within the first week, LDL and HDL were still elevated after 2 weeks upon HFD. Importantly, we found that hypothalamic PSA removal aggravated LDL elevation and reduced HDL levels upon HFD. These results indicate that hypothalamic PSA controls plasma lipoprotein profile by circumventing the rise of LDL-to-HDL cholesterol ratio in plasma during overfeeding. Although mechanisms by which hypothalamic PSA controls plasma cholesterol homeostasis remains to be elucidated, these findings also suggest that low level of hypothalamic PSA might be a risk factor for dyslipidemia and cardiovascular diseases.

Docosahexaenoic acid (DHA; 22: 6 omega-3) is highly enriched in the brain and is required for proper brain development and function. Its deficiency has been shown to be linked with the emergence of neurological diseases. Dietary omega-3 fatty acid supplements including DHA have been suggested to improve neuronal development and enhance cognitive functions. Findings suggested that DHA is better incorporated into the brain when esterified at the sn-2 position of a lysophosphatidylcholine (LysoPC-DHA). AceDoPC (R) is a structured phospholipid or acetyl-LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC (R) is a specific and preferred carrier of DHA to the brain. When AceDoPC (R) was injected to rats that were subjected to an ischemic stroke, it prevents the extension of brain lesions. Regarding the essential role of DHA for cerebral functions, targeting the brain with specific carriers of DHA might provide novel therapeutic approaches to neurodegenerative diseases., Captage sélectif du DHA par le cerveau à partir d’un phospholipide structuré, l’AceDoPC®. L’acide docosahexaénoïque (22:6v-3,DHA) est l’acide gras le plus abondant de la sphère cérébro-vasculaire et il est nécessaire au développement cérébral et à l’apprentissage. Par ailleurs, unediminution de la concentration cérébrale en DHAest observée chez les patients souffrant de maladies neurodégénératives. Différentes études réalisées chez l’animal et l’Homme suggèrent qu’un apport nutritionnel adéquat en acides gras polyinsaturés v-3 et surtout en DHA peut prévenir le déclin cognitif et atténuer les perturbations physiologiques du cerveau associés à l’âgeouauxmaladiesneurologiques.LeDHApeut être apporté aucerveau sousdifférentes formes, la lysophosphatidylcholine (LysoPC) possédant duDHAen position sn-2 étant une forme d’apport privilégiée et spécifique deDHAau cerveau. L’AceDoPC® est un phospholipide structuré correspondant à l’acétyl-LysoPCDHAqui est une forme stabilisée de la forme physiologiqueLysoPC.Nos étudesmontrent que l’AceDoPC® est un transporteur privilégié et spécifique du DHA au cerveau comme la forme physiologique LysoPC. Nous montrons des effets neuro-protecteurs de l’AceDoPC® sur un accident vasculaire cérébral induit chez le rat avec une réduction significative de la taille des lésions. En considérant les rôles essentiels du DHA pour le cerveau, cette nouvelle approche de ciblage cérébral du DHA offre des perspectives prometteuses dans le développement de stratégies préventives et thérapeutiques pour les maladies neurologiques.

Article en libre accès; Women and men, female and male animals and cells are biologically different, and acknowledgement of this fact is critical to advancing medicine. However, incorporating concepts of sex-specific analysis in basic research is largely neglected, introducing bias into translational findings, clinical concepts and drug development. Research funding agencies recently approached these issues but implementation of policy changes in the scientific community is still limited, probably due to deficits in concepts, knowledge and proper methodology. This expert review is based on the EUGenMed project (www.eugenmed.eu) developing a roadmap for implementing sex and gender in biomedical and health research. For sake of clarity and conciseness, examples are mainly taken from the cardiovascular field that may serve as a paradigm for others, since a significant amount of knowledge how sex and oestrogen determine the manifestation of many cardiovascular diseases (CVD) has been accumulated. As main concepts for implementation of sex in basic research, the study of primary cell and animals of both sexes, the study of the influence of genetic vs. hormonal factors and the analysis of sex chromosomes and sex specific statistics in genome wide association studies (GWAS) are discussed. The review also discusses methodological issues, and analyses strength, weaknesses, opportunities and threats in implementing sex-sensitive aspects into basic research.

Nowadays, human brain activity in response to complex paradigms can be extensively mapped. Though introduced relatively recently, functional magnetic resonance imaging (fMRI) based on blood-oxygen-level-dependent contrast has developed dramatically. It is a noninvasive and exploratory approach which provides in a relatively direct way a differentiated measure of each processing step within the brain, the complete network giving access to cognitive mechanisms. Compared with the other functional imaging methods, fMRI offers high spatial and temporal resolution, and so can detail cognitive tasks both in space and in time by following the time course of the operations. This review deals with how this detailed breakdown is achieved. A further aim is to show how and why fMRI can be used to study sensory perceptions that might, at first sight, seem hard to address by this method, namely perceptions during eating. The processing of stimuli from food by the brain is one determinant of food representation, but also of food liking and wanting, which in turn control appetite, and ultimately food intake. Food consumption also activates the reward system, which thus helps to control food intake. fMRI experiments conducted with human subjects have largely helped to gain a fuller understanding of these intricate brain processes. Among the sensations triggered by food, visual, olfactory, gustatory, and somatosensory cues are the most salient. Accordingly, we focus here on these sensory systems and on the integration of the two senses necessary to produce flavor perception: namely olfaction and gustation.

International audience; Blood Oxygenation Level Dependent functional MRI (BOLD fMRI) during electrical paw stimulation has been widely used in studies aimed at the understanding of the somatosensory network in rats. However, despite the well-established anatomical connections between corti-cal and subcortical structures of the sensorimotor system, most of these functional studies have been concentrated on the cortical effects of sensory electrical stimulation. BOLD fMRI study of the integration of a sensorimotor input across the sensorimotor network requires an appropriate methodology to elicit functional activation in cortical and subcortical areas owing to the regional differences in both neuronal and vascular architectures between these brain regions. Here, using a combination of low level anesthesia, long pulse duration of the electrical stimulation along with improved spatial and temporal signal to noise ratios, we provide a functional description of the main cortical and subcortical structures of the sensorimotor rat brain. With this calibrated fMRI protocol, unilateral non-noxious sensorimotor electrical hind-paw stimulation resulted in robust positive activations in the contralateral sensorimotor cortex and bilaterally in the sensorimotor thalamus nuclei, whereas negative activations were observed bilaterally in the dorsolateral caudate-putamen. These results demonstrate that, once the experimental setup allowing necessary spatial and temporal signal to noise ratios is reached , hemodynamic changes related to neuronal activity, as preserved by the combination of a soft anesthesia with a soft muscle relaxation, can be measured within the sensorimotor network. Moreover, the observed responses suggest that increasing pulse duration of the electrical stimulus adds a proprioceptive component to the sensory input that activates sen-sorimotor network in the brain, and that these activation patterns are similar to those induced by digits paw's movements. These findings may find application in fMRI studies of sensori-motor disorders within cortico-basal network in rodents.

In this article, we suggest that the « capable body » concept can be introduced at the crossroads of an evolutionist and a neurobiological points of view. The ability of the human specie to create, learn and disseminate technical skills (body and technical knowhow), became a decisive selective advantage. The neurobiological component of this advantage originates not only from a global increase of the cerebral volume, but rather from the properties and efficiency of specific neuronal populations. These neurons are involved in the learning and diffusion of technical skills (cerebellum, mirror neurons) but also in the integration of the tools in the sensitive body (bimodal neurons). Thus, the human being inherits phylogenetically and epi-phylogenetically an “able body” which extends the biological body. The able body is versatile and polymorphic, changing with the grasping and releasing of the required tool., Il est question dans cette article de synthèse de montrer que le concept de corps capacitaire peut tout à fait prendre sa place dans une perspective intégrant des connaissances concernant à la fois l’évolution de l’espèce humaine et le cerveau de l’homme contemporain. La capacité de l’espèce humaine à créer, apprendre et transmettre des savoir-faire (utilisant des techniques du corps ou des aides techniques), s’est avérée constituer un avantage sélectif déterminant. La composante neurobiologique de cet avantage n’a sans doute pas seulement pour origine une augmentation globale du volume cérébral, mais semble surtout provenir des propriétés et de l’efficacité de certaines populations de neurones. Ces neurones sont impliqués dans l’apprentissage des techniques et la diffusion des savoirs techniques (cervelet, neurones miroirs) mais aussi dans l’intégration de l’outil au corps sensible (neurones bimodaux). Ainsi, l’individu humain hérite phylogénétiquement et épi-phylogénétiquement d’un corps capacitaire dont le corps biologique n’est que le substrat. Ce corps capacitaire est changeant et polymorphe, au gré des outils saisis et déposés.

Dans cet article, nous présentons des études récentes de neuro-imagerie destinées à identifier le réseau neuronal impliqué dans l’écriture manuscrite. Ces études, réalisées chez l’adulte et chez l’enfant, montrent que la maitrise de l’écriture manuscrite repose sur la mise en jeu d’un réseau de structures cérébrales dont l’implication et l’interconnexion sont spécifiques de l’écriture des caractères alphabétiques, se construisent au cours de l’apprentissage conjoint de l’écriture et de la lecture et dépendent du niveau d’expertise du scripteur. En outre, une partie de ce réseau graphomoteur est aussi mise en jeu au cours de l’identification des lettres sur base visuelle et de la lecture. Ces compétences graphomotrices servent également de base au développement d’activités plus complexes impliquant les connaissances orthographiques et la composition de textes. Les études présentées ici sont abordées de deux perspectives, celles des neurosciences et de la recherche en psychologie cognitive, car elles s’avèrent toutes deux nécessaires pour comprendre un processus aussi complexe que l’écriture, à la fois tributaire d’interactions naturelles et éducationnelles. - In this article, we present recent neuroimaging studies performed to identify the neural network involved in handwriting. These studies, carried out in adults and in children, suggest that the mastery of handwriting is based on the involvement of a network of brain structures whose involvement and inter-connection are specific to writing alphabet characters. This network is built upon the joint learning of writing and reading and depends on the level of expertise of the writer. In addition, a part of this graphomotor network is also brought into play during the identification letters during visual reading. These skills are also the basis for the development of more complex language activities involving orthographic knowledge and composition of texts. The studies presented cover two perspectives: that of neuroscience and that of cognitive psychology, as both are necessary to understand a complex process of writing and both depend on natural interactions and the influence of educational exposure.

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially inuenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use.; Il s'agit d'explorer la relation entre dose de radiofréquences reçue ds le cerveau lors de l'utilisation de téléphone mobile et la survenue de tumeurs du cerveau.

A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets (P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat and -sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets' blood lipid levels, microbiota activity, gut-brain axis, and neurocognitive abilities after weaning.-Val-Laillet, D., Besson, M., Guerin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huerou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

International audience; Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging.

International audience; The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin. Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops. Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. This review summarizes our present knowledge on brain sites where the endogenous opioid system controls hedonic responses and is modified in response to drugs of abuse in the rodent brain. We review 1) the latest data on the anatomy of the opioid system, 2) the consequences of local intracerebral pharmacological manipulation of the opioid system on reinforced behaviors, 3) the consequences of gene knockout on reinforced behaviors and drug dependence, and 4) the consequences of chronic exposure to drugs of abuse on expression levels of opioid system genes. Future studies will establish key molecular actors of the system and neural sites where opioid peptides and receptors contribute to the onset of addictive disorders. Combined with data from human and nonhuman primate (not reviewed here), research in this extremely active field has implications both for our understanding of the biology of addiction and for therapeutic interventions to treat the disorder.

39 pages, 4 figures; International audience; While questions of a functional localization of consciousness in the brain have been the subject of myriad studies, the idea of a temporal access code as a specific brain mechanism for consciousness has remained a neglected possibility. Dresp-Langley and Durup (2009, 2012) proposed a theoretical approach in terms of a temporal access mechanism for consciousness based on its two universally recognized properties. Consciousness is limited in processing capacity and described by a unique processing stream across a single dimension, which is time. The time ordering function of conscious states is highlighted and neurobiological theories of the temporal brain activities likely to underlie such function are discussed, and the properties of the code model are then introduced. Spatial information is integrated into provisory topological maps at non-conscious levels through adaptive resonant matching, but does not form part of the temporal access code as such. The latter, de-correlated from the spatial code, operates without any need for firing synchrony on the sole basis of temporal coincidence probabilities in dedicated resonant circuits through progressively non-arbitrary selection of specific temporal activity patterns in the continuously developing brain.

Three areas in the brain continuously generate new neurons throughout life: the subventricular zone lining the lateral ventricles, the dentate gyrus in the hippocampus and the median eminence in the hypothalamus. These areas harbour neural stem cells, which contribute to neural repair by generating daughter cells that then become functional neurons or glia. Impaired neurogenesis leads to detrimental consequences, such as depression, decline of cognitive abilities and obesity. Adult neurogenesis is a versatile process that can be modulated either positively or negatively by many effectors, external or endogenous. Diet can modify neurogenesis both ways, either directly by ways of food-borne molecules, or possibly by the modifications induced on gut microbiota composition. It is therefore critical to define dietary strategies optimal for the maintenance of the stem cell pools.

Docosahexaenoic acid (DHA; 22:6 omega-3) is highly enriched in the brain and is required for proper brain development and function. Its deficiency has been shown to be linked with the emergence of neurological diseases. Dietary omega-3 fatty acid supplements including DHA have been suggested to improve neuronal development and enhance cognitive functions. However, mechanisms of DHA incorporation in the brain remain to be fully understood. Findings suggested that DHA is better incorporated when esterified within lysophospholipid rather than under its non-esterified form. Furthermore, DHA has the potential to be converted into diverse oxylipins with potential neuroprotective effects. Since DHA is poorly synthesized de novo, targeting the brain with specific carriers of DHA might provide novel therapeutic approaches to neurodegenerative diseases.

International audience; Several genetic causes of autism spectrum disorder (ASD) have been identified. However, more recent work has highlighted that certain environmental exposures early in life may also account for some cases of autism. Environmental insults during pregnancy, such as infection or malnutrition, seem to dramatically impact brain development. Maternal viral or bacterial infections have been characterized as disruptors of brain shaping, even if their underlying mechanisms are not yet fully understood. Poor nutritional diversity, as well as nutrient deficiency, is strongly associated with neurodevelopmental disorders in children. For instance, imbalanced levels of essential fatty acids, and especially polyunsaturated fatty acids (PUFAs), are observed in patients with ASD and other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder (ADHD) and schizophrenia). Interestingly, PUFAs, and specifically n-3 PUFAs, are powerful immunomodulators that exert anti-inflammatory properties. These prenatal dietary and immunologic factors not only impact the fetal brain, but also affect the microbiota. Recent work suggests that the microbiota could be the missing link between environmental insults in prenatal life and future neurodevelopmental disorders. As both nutrition and inflammation can massively affect the microbiota, we discuss here how understanding the crosstalk between these three actors could provide a promising framework to better elucidate ASD etiology.

Brain imaging data are available on the DRYAD public repository: http://dx.doi.org/10.5061/dryad.ck3g3.; International audience; Brain responses to feed flavors with or without a feed additive (FA) were investigated in piglets familiarized or not with this FA. Sixteen piglets were allocated to 2 dietary treatments from weaning until d 37: the naive group (NAI) received a standard control feed and the familiarized group (FAM) received the same feed added with a FA mainly made of orange extracts. Animals were subjected to a feed transition at d 16 post-weaning, and to 2-choice feeding tests at d 16 and d 23. Production traits of the piglets were assessed up to d 28 post-weaning. From d 26 onwards, animals underwent 2 brain imaging sessions (positron emission tomography of 18FDG) under anesthesia to investigate the brain activity triggered by the exposure to the flavors of the feed with (FA) or without (C) the FA. Images were analyzed with SPM8 and a region of interest (ROI)-based small volume correction (p < 0.05, k ≥ 25 voxels per cluster). The brain ROI were selected upon their role in sensory evaluation, cognition and reward, and included the prefrontal cortex, insular cortex, fusiform gyrus, limbic system and corpus striatum. The FAM animals showed a moderate preference for the novel post-transition FA feed compared to the C feed on d 16, i.e., day of the feed transition (67% of total feed intake). The presence or absence of the FA in the diet from weaning had no impact on body weight, average daily gain, and feed efficiency of the animals over the whole experimental period (p ≥ 0.10). Familiar feed flavors activated the prefrontal cortex. The amygdala, insular cortex, and prepyriform area were only activated in familiarized animals exposed to the FA feed flavor. The perception of FA feed flavor in the familiarized animals activated the dorsal striatum differently than the perception of the C feed flavor in naive animals. Our data demonstrated that the perception of FA in familiarized individuals induced different brain responses in regions involved in reward anticipation and/or perception processes than the familiar control feed flavor in naive animals. Chronic exposure to the FA might be necessary for positive hedonic effects, but familiarity only cannot explain them.

With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new nutritional approaches to prevent and delay the onset of cognitive decline. Neuroinflammatory processes contribute to neuronal damage that underpins neurodegenerative disorders. Growing evidence sheds light on the use of dietary n-3 long chain polyunsaturated fatty acids to improve cognitive performances and reduce the neuroinflammatory responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in cognitive disorders. We will also discuss the mechanisms underlying n-3 polyunsaturated fatty acids effect on neuroinflammation and memory decline., Le développement d’approches nutritionnelles pertinentes pour prévenir et retarder l’apparition du déclin cognitif est un enjeu important, compte tenu du vieillissement de la population et de l’augmentation de l’incidence des maladies neurodégénératives. Les processus neuro-inflammatoires contribuent aux mécanismes neuropathologiques impliqués dans les troubles neurodégénératifs et de la cognition. Des données récentes indiquent l’importance des acides gras polyinsaturés n-3 alimentaires dans le maintien des performances mnésiques et la régulation de la neuroinflammation liée à l’âge ou à la maladie d’Alzheimer. Dans cette revue, seront présentées des données récentes sur les liens existants entre le statut nutritionnel en acides gras polyinsaturés n-3, les processus neuro-inflammatoires et les troubles cognitifs associés, ainsi que les mécanismes qui pourraient être impliqués dans les effets protecteurs de ces acides gras.

Among omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA, 22:6n-3) is important for adequate brain development and cognition. DHA is highly concentrated in the brain and plays an essential role in brain functioning. DHA, one of the major constituents in fish fats, readily crosses the blood brain barrier from blood to the brain. Its critical role was further supported by its reduced levels in the brain of Alzheimer's disease (AD) patients. This agrees with a potential role of DHA in memory, learning and cognitive processes. Since there is yet no cure for dementia such as AD, there is growing interest in the role of DHA-supplemented diet in the prevention of AD pathogenesis. Accordingly, animal, epidemiological, preclinical and clinical studies indicated that DHA has neuroprotective effects in a number of neurodegenerative conditions including AD. The beneficial effects of this key omega-3 fatty acid supplementation may depend on the stage of disease progression, other dietary mediators and the apolipoprotein ApoE genotype. Herein, our review investigates, from animal and cell culture studies, the molecular mechanisms involved in the neuroprotective potential of DHA with emphasis on AD.

International audience; For different functional magnetic resonance imaging experiments using blood oxygenation level-dependent (BOLD) contrast, the acquisition of T2*-weighted scans at a high spatial resolution may be advantageous in terms of time-course signal-to-noise ratio and of BOLD sensitivity when the regions are prone to susceptibility artifacts. In this study, we explore this solution by examining how spatial resolution influences activations elicited when appetizing food pictures are viewed. Twenty subjects were imaged at 3 T with two different voxel volumes, 3.4 μl and 27 μl. Despite the diminution of brain coverage, we found that high-resolution acquisition led to a better detection of activations. Though known to suffer to different degrees from susceptibility artifacts, the activations detected by high spatial resolution were notably consistent with those reported in published activation likelihood estimation metaanalyses, corresponding to taste-responsive regions. Furthermore, these regions were found activated bilaterally, in contrast with previous findings. Both the reduction of partial volume effect, which improves BOLD contrast, and the mitigation of susceptibility artifact, which boosts the signal to noise ratio in certain regions, explained the better detection noted with high resolution. The present study provides further evidences that high spatial resolution is a valuable solution for human BOLD fMRI, especially for studying food-related stimuli.

Background: Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study. Methods: Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix were assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the diagnosis/reference date. Results: There were 3,761 included brain tumor cases (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1 to 4 years before the diagnosis/reference date and glioma [odds ratio (OR) ≥ 90th percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36–2.07; PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97–1.57; PLinear trend = 0.02). Conclusions: Results showed positive associations between ELF in the recent past and glioma. Impact: Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumorigenesis. Cancer Epidemiol Biomarkers Prev; 23(9); 1863–72. ©2014 AACR.

International audience; The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography ((99m)Tc-HMPAO) further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow changes in brain regions known to be involved in memory, reward processes and hedonic (i.e., pleasure) evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus, and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation.

Background The neuropeptide Kiss and its receptor KissR are key-actors in the brain control of reproduction in mammals, where they are responsible for the stimulation of the activity of GnRH neurones. Investigation in other vertebrates revealed up to 3 Kiss and 4 KissR paralogs, originating from the two rounds of whole genome duplication in early vertebrates. In contrast, the absence of Kiss and KissR has been suggested in birds, as no homologs of these genes could be found in current genomic databases. This study aims at addressing the question of the existence, from an evolutionary perspective, of the Kisspeptin system in birds. It provides the first large-scale investigation of the Kisspeptin system in the sauropsid lineage, including ophidian, chelonian, crocodilian, and avian lineages. Results Sauropsid Kiss and KissR genes were predicted from multiple genome and transcriptome databases by TBLASTN. Phylogenetic and syntenic analyses were performed to classify predicted sauropsid Kiss and KissR genes and to re-construct the evolutionary scenarios of both gene families across the sauropsid radiation. Genome search, phylogenetic and synteny analyses, demonstrated the presence of two Kiss genes (Kiss1 and Kiss2 types) and of two KissR genes (KissR1 and KissR4 types) in the sauropsid lineage. These four genes, also present in the mammalian lineage, would have been inherited from their common amniote ancestor. In contrast, synteny analyses supported that the other Kiss and KissR paralogs are missing in sauropsids as in mammals, indicating their absence in the amniote lineage. Among sauropsids, in the avian lineage, we demonstrated the existence of a Kiss2-like gene in three bird genomes. The divergence of these avian Kiss2-like sequences from those of other vertebrates, as well as their absence in the genomes of some other birds, revealed the processes of Kiss2 gene degeneration and loss in the avian lineage. Conclusion These findings contribute to trace back the evolutionary history of the Kisspeptin system in amniotes and sauropsids, and provide the first molecular evidence of the existence and fate of a Kiss gene in birds.

Kisspeptin (KP) neurones in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co-synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and processes. GnRH neurones not only form the final output pathway regulating the reproductive functions of the anterior pituitary gland, but also provide neuronal input to sites within the hypothalamus. The current double-label immunohistochemical studies investigated whether GnRH-immunoreactive (IR) projections to the RP3V and/or Arc establish morphological connections with KP-IR neurones at these sites. To optimise visualisation of KP immunoreactivity in, respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX oil-treated female mice were studied. Confocal laser microscopic analysis of immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish asymmetric synaptic contacts, which usually reflect excitatory neurotransmission, with KP-IR neurones in both the RP3V and Arc. Together with previous data, these findings indicate reciprocal connectivity between both of the KP cell populations and the GnRH neuronal system. The functional significance of the GnRH-IR input to the two separate KP cell populations requires electrophysiological investigation.

Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development.

International audience; Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress.

L’expansion des neurosciences a conduit certains neurologues et psychiatres à repenser l’idée d’une fusion de leurs spécialités au sein d’une discipline neuropsychiatrique commune. A partir de l’ethnographie du développement d’une technologie thérapeutique pour des troubles neurologiques et psychiatriques par une équipe de neurosciences, cet article analyse en quoi ce projet interroge le statut épistémologique de la psychiatrie, de ses méthodes et de ses objets. Il décrit les différents dispositifs de recherche et de soin au sein desquels neurologues et psychiatres collaborent ainsi que les formes de pratiques, figures du malade et définitions des troubles qui en émergent. Si la technologie autorise l’ouverture de lieux de pratique communs, l’interrogation symétrique d’événements et la translation de problématiques entre les acteurs, le projet neuropsychiatrique se heurte cependant dans le soin à l’irréductibilité de la définition du trouble et du patient psychiatriques à la focale biologique. The rise of neurosciences has led certain neurologists and psychiatrists to consider the idea of the merger of their clinical specialties in a common neuropsychiatric discipline. Based on an ethnography of the use of a therapeutic technology for the treatment of neurological and psychiatric disorders in a neuroscience center, this article explores the epistemological status of psychiatry, its methods and its objects. I describe the research and therapeutic organizations within which neurologists and psychiatrists collaborate and the forms of practices, perspectives of patients and disorder definitions that are shaped therein. The technology opens common spaces of practice for the actors. It also creates an opportunity for psychiatry and neurology to provide symmetrical questionings of clinical events. However, the neuropsychiatric project appears to be bounded by the irreducibility of the psychiatric patient and disorder to biological determinism.

This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d.) infusions of 15% glucose (F(Glu)), lithium chloride (F(LiCl)), or saline (control treatment, F(NaCl)). One and five weeks later, the animals were subjected to three two-choice feeding tests without reinforcement to check the acquisition of a conditioned flavour preference or aversion. In between, the anaesthetised pigs were subjected to three (18)FDG PET brain imaging coupled with an olfactogustatory stimulation with the conditioned flavours. During conditioning, the pigs spent more time lying inactive, and investigated their environment less after the F(LiCl) than the F(NaCl) or F(Glu) meals. During the two-choice tests performed one and five weeks later, the F(NaCl) and F(Glu) foods were significantly preferred over the F(LICl) food even in the absence of i.d. infusions. Surprisingly, the F(NaCl) food was also preferred over the F(Glu) food during the first test only, suggesting that, while LiCl i.d. infusions led to a strong flavour aversion, glucose infusions failed to induce flavour preference. As for brain imaging results, exposure to aversive or less preferred flavours triggered global deactivation of the prefrontal cortex, specific activation of the posterior cingulate cortex, as well as asymmetric brain responses in the basal nuclei and the temporal gyrus. In conclusion, postingestive visceral stimuli can modulate the flavour/food hedonism and further feeding choices. Exposure to flavours with different hedonic values induced metabolism differences in neural circuits known to be involved in humans in the characterization of food palatability, feeding motivation, reward expectation, and more generally in the regulation of food intake.

The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT) and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus) as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus), as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

International audience; Rainbow trout, Oncorhynchus mykiss, is an important aquaculture species worldwide and, in addition to being of commercial interest, it is also a research model organism of considerable scientific importance. Because of the lack of a whole genome sequence in that species, transcriptomic analyses of this species have often been hindered. Using next-generation sequencing (NGS) technologies, we sought to fill these informational gaps. Here, using Roche 454-Titanium technology, we provide new tissue-specific cDNA repertoires from several rainbow trout tissues. Non-normalized cDNA libraries were constructed from testis, ovary, brain and gill rainbow trout tissue samples, and these different libraries were sequenced in 10 separate half-runs of 454-Titanium. Overall, we produced a total of 3 million quality sequences with an average size of 328 bp, representing more than 1 Gb of expressed sequence information. These sequences have been combined with all publicly available rainbow trout sequences, resulting in a total of 242,187 clusters of putative transcript groups and 22,373 singletons. To identify the predominantly expressed genes in different tissues of interest, we developed a Digital Differential Display (DDD) approach. This approach allowed us to characterize the genes that are predominantly expressed within each tissue of interest. Of these genes, some were already known to be tissue-specific, thereby validating our approach. Many others, however, were novel candidates, demonstrating the usefulness of our strategy and of such tissue-specific resources. This new sequence information, acquired using NGS 454-Titanium technology, deeply enriched our current knowledge of the expressed genes in rainbow trout through the identification of an increased number of tissue-specific sequences. This identification allowed a precise cDNA tissue repertoire to be characterized in several important rainbow trout tissues. The rainbow trout contig browser can be accessed at the following publicly available web site (http://www.sigenae.org/).

Background Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. Methods In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Wide-Range-Achievement-Test (WRAT-3) to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ). Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales) and potential confounders (age, sex, education, income). Results Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p < 0.01. Conclusions Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology.

Recent evidence suggests that interleukin-1beta (IL-1beta), which was originally identified as a proinflammatory cytokine, is also required in the brain for memory processes. We have previously shown that IL-1beta synthesis in the hippocampus is dependent on P2X(7) receptor (P2X(7)R), which is an ionotropic receptor of ATP. To substantiate the role of P2X(7)R in both brain IL-1beta expression and memory processes, we examined the induction of IL-1beta mRNA expression in the hippocampus of wild-type (WT) and homozygous P2X(7) receptor knockout mice (P2X(7)R(-/-)) following a spatial memory task. The spatial recognition task induced both IL-1beta mRNA expression and c-Fos protein activation in the hippocampus of WT but not of P2X(7)R(-/-) mice. Remarkably, P2X(7)R(-/-) mice displayed spatial memory impairment in a hippocampal-dependant task, while their performances in an object recognition task were unaltered. Taken together, our results show that P2X(7)R plays a critical role in spatial memory processes and the associated hippocampal IL-1beta mRNA synthesis and c-Fos activation.