Abnormal wiring of CCK⁺ basket cells disrupts spatial information coding

The function of cortical GABAergic interneurons is largely determined by their integration into specific neural circuits, but the mechanisms controlling the wiring of these cells remain largely unknown. This is particularly true for a major population of basket cells that express the neuropeptide cholecystokinin (CCK). Here we found that the tyrosine kinase receptor ErbB4 was required for the normal integration into cortical circuits of basket cells expressing CCK and vesicular glutamate transporter 3 (VGlut3). The number of inhibitory synapses made by CCK+VGlut3+ basket cells and the inhibitory drive they exerted on pyramidal cells were reduced in conditional mice lacking ErbB4. Developmental disruption of the connectivity of these cells diminished the power of theta oscillations during exploratory behavior, disrupted spatial coding by place cells, and caused selective alterations in spatial learning and memory in adult mice. These results suggest that normal integration of CCK+ basket cells in cortical networks is key to support spatial coding in the hippocampus.Supported by grants from Fundación Alicia Koplowitz and the European Research Council (ERC-2012-StG 310021) to B.R., from the European Research Council (ERC-2011-AdG 293683) to O.M., from the Spanish G293683overnment (CONSOLIDER CSD2007-00023) and Lilly Research Awards Program to B.R. and O.M, and from the French government (ANR-10-EQX-008-1 to A.M. and LabEX BRAIN ANR-10-LABX-43 to A.F. and A.M.). O.M. and B.R. are Wellcome Trust Investigators.Peer reviewe

Age-related impairment of declarative memory: linking memorization of temporal associations to GluN2B redistribution in dorsal CA1

GluN2B subunits of NMDA receptors have been proposed as a target for treating age‐related memory decline. They are indeed considered as crucial for hippocampal synaptic plasticity and hippocampus‐dependent memory formation, which are both altered in aging. Because a synaptic enrichment in GluN2B is associated with hippocampal LTP in vitro, a similar mechanism is expected to occur during memory formation. We show instead that a reduction of GluN2B synaptic localization induced by a single‐session learning in dorsal CA1 apical dendrites is predictive of efficient memorization of a temporal association. Furthermore, synaptic accumulation of GluN2B, rather than insufficient synaptic localization of these subunits, is causally involved in the age‐related impairment of memory. These challenging data identify extra‐synaptic redistribution of GluN2B‐containing NMDAR induced by learning as a molecular signature of memory formation and indicate that modulating GluN2B synaptic localization might represent a useful therapeutic strategy in cognitive aging

Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians

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Modifications de l'activite des neurones cholinergiques septo-hippocampiques induites par les activites mnesiques chez la souris: signification fonctionnelle et identification des mecanismes de controle septal

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 79784 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Adaptive emotional memory: the key hippocampal-amygdalar interaction

For centuries philosophical and clinical studies have emphasized a fundamental dichotomy between emotion and cognition, as, for instance, between behavioral/emotional memory and explicit/representative memory. However, the last few decades cognitive neuroscience have highlighted data indicating that emotion and cognition, as well as their underlying neural networks, are in fact in close interaction. First, it turns out that emotion can serve cognition, as exemplified by its critical contribution to decision-making or to the enhancement of episodic memory. Second, it is also observed that reciprocally cognitive processes as reasoning, conscious appraisal or explicit representation of events can modulate emotional responses, like promoting or reducing fear. Third, neurobiological data indicate that reciprocal amygdalar-hippocampal influences underlie such mutual regulation of emotion and cognition. While supporting this view, the present review discusses experimental data, obtained in rodents, indicating that the hippocampal and amygdalar systems not only regulate each other and their functional outcomes, but also qualify specific emotional memory representations through specific activations and interactions. Specifically, we review consistent behavioral, electrophysiological, pharmacological, biochemical and imaging data unveiling a direct contribution of both the amygdala and hippocampal-septal system to the identification of the predictor of a threat in different situations of fear conditioning. Our suggestion is that these two brain systems and their interplay determine the selection of relevant emotional stimuli, thereby contributing to the adaptive value of emotional memory. Hence, beyond the mutual quantitative regulation of these two brain systems described so far, we develop the idea that different activations of the hippocampus and amygdala, leading to specific configurations of neural activity, qualitatively impact the formation of emotional memory representations, thereby producing either adaptive or maladaptive fear memories

Supplémentation nutritionnelle en vitamine A (effets sur les déficits fonctionnels hippocampiques et le déclin mnésique liés à l'âge)

Un ensemble de données cohérentes suggèrent que l'acide rétinoïque (AR, métabolite actif de la vitamine A), en régulant l'expression de nombreux génes codant pour des protéines neuronales spécifiques, intervient dans les processus de plasticité synaptique qui sous-tendent l'élaboration et la conservation de représentations mnésiques. Cette hypothèse a été confortée par des résultats récents qui montrent un lien entre des déficits de mémoire relationnelle chez l'animal âgé et une baisse du niveau d'activité de la voie de signalisation des rétinoïdes. Des résultats comparables ont été obtenus chez des souris carencées en vitamine A (Etchamendy et al., 2001, 2003). L'objectif de ce travail était de donner de nouvelles perspectives concernant ce lien entre niveau d'activité de la voie des rétinoïdes et capacités mnésiques au cours du vieillissement. Notre approche s'est principalement focalisée sur deux questions : (i) dans quelle mesure une approche par supplémentaion nutritionnelle en vitamine A est-elle susceptible d'améliorer les performances mnésiques d'animaux âgés en maintenant le niveau d'activité de la voie de signalisation des rétinoïdes ? (ii) pouvons nous préciser quels sont les systèmes neurobiologiques qui, sous l'influence de la vitamine A, sous-tendent l'amélioration de ces performances ? Nos résultats montrent qu'une supplémentation alimentaire en vitamine A permet de prévenir le déclin mnésique d'animaux âgés en mémoire relationnelle et de travail, tout en maintenant le niveau d'activité de la voie de signalisation de l'AR dans l'hippocampe. Par ailleurs, ils soulignent le rôle de l'hippocampe dans la formation et l'expression de ces deux types de mémoire et permettent de mettre en avant l'implication possible des rétinoïdes dans l'activité et le fonctionnement de cette structure. Nos résultats contribuent à mieux comprendre le rôle des rétinoïdes sur la formation hippocampique et suggèrent l'utilisation d'une approche nutritionnel pour prévenir les troubles mnésiques liés à l'âge.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

False Opposing Fear Memories Are Produced as a Function of the Hippocampal Sector Where Glucocorticoid Receptors Are Activated

International audienceInjection of corticosterone (CORT) in the dorsal hippocampus (DH) can mimic post-traumatic stress disorder (PTSD)—related memory in mice: both maladaptive hypermnesia for a salient but irrelevant simple cue and amnesia for the traumatic context. However, accumulated evidence indicates a functional dissociation within the hippocampus such that contextual learning is primarily associated with the DH whereas emotional processes are more linked to the ventral hippocampus (VH). This suggests that CORT might have different effects on fear memories as a function of the hippocampal sector preferentially targeted and the type of fear learning (contextual vs. cued) considered. We tested this hypothesis in mice using CORT infusion into the DH or VH after fear conditioning, during which a tone was either paired (predicting-tone) or unpaired (predicting-context) with the shock. We first replicate our previous results showing that intra-DH CORT infusion impairs contextual fear conditioning while inducing fear responses to the not predictive tone. Second, we show that, in contrast, intra-VH CORT infusion has opposite effects on fear memories: in the predicting-tone situation, it blocks tone fear conditioning while enhancing the fear responses to the context. In both situations, a false fear memory is formed based on an erroneous selection of the predictor of the threat. Third, these opposite effects of CORT on fear memory are both mediated by glucocorticoid receptor (GR) activation, and reproduced by post-conditioning stress or systemic CORT injection. These findings demonstrate that false opposing fear memories can be produced depending on the hippocampal sector in which the GRs are activated. © Copyright © 2020 Kaouane, Ducourneau, Marighetto, Segal and Desmedt

Preventing and treating PTSD-like memory by trauma contextualization

International audiencePost-traumatic stress disorder (PTSD) is characterized by emotional hypermnesia on which preclinical studies focus so far. While this hypermnesia relates to salient traumatic cues, partial amnesia for the traumatic context can also be observed. Here, we show in mice that contextual amnesia is causally involved in PTSD-like memory formation, and that treating the amnesia by re-exposure to all trauma-related cues cures PTSD-like hypermnesia. These findings open a therapeutic perspective based on trauma contextualization and the underlying hippocampal mechanisms

Effect of learning on slow gamma propagation between hippocampus and cortex in the wild-type and AD mice

Abstract Slow gamma oscillations (20–50 Hz) have been suggested to coordinate information transfer between brain structures involved in memory formation. Whereas the involvement of slow gamma in memory processing was studied by means of correlation between the gamma power and the occurrence of a given event (sharp wave ripples (SWRs), cortical transients), our approach consists of the analysis of the transmission of slow gamma itself. We use the method based on Granger causality principle—direct Directed Transfer Function, which allows to determine directed propagation of brain activity, including bidirectional flows. Four cortical sites along with CA1 ipsi- and contralateral were recorded in behaving wild-type and APP/PS1 mice before and after learning session of a spatial memory task. During slow wave sleep propagation of slow gamma was bidirectional, forming multiple loops of interaction which involved both CA1 and some of cortical sites. In episodes coincident with SWRs the number and strength of connectivity pathways increased in both groups compared to episodes without SWRs. The effect of learning was expressed only in APP/PS1 mice and consisted in strengthening of the slow gamma transmission from hippocampus to cortex as well as between both CA1 which may serve more efficient transmission of information from impaired CA1

Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response

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