Hippocampal activity related to social stimuli in a mouse model os ASD.
Lieu : Salle des séminaires, Bâtiment B2, Université de Bordeaux, Avenue des facultés, 33600 Pessac
Superviseur : Yoon Cho (INCIA)
Abstract
Autism Spectrum Disorders (ASD) represent a neurodevelopmental disease affecting about 1% of the population. Core symptoms displayed by patients are medium to severe deficits in social interaction, limited center of interest, repetitive behavior as well as intellectual and/or cognitive deficiencies. Recent progress in human genetics enabled the identification of several susceptibility genes; many of them share common and prominent roles in the synapse. Deletion and de novo mutations of the SHANK3 gene have been associated in humans with severe forms of ASD, yet, the functional consequences of these mutations on neural integrity and behavioral disturbances remain largely unknown.
Mice carrying SHANK3 exon-21 deletion (Shank3(ΔC/ΔC) display social deficits and significant neurophysiological alterations such as synaptic abnormalities, in particular, in the hippocampus, a place of intense neuroplasticity during neurodevelopment and learning and memory process. Interestingly, even though hippocampal vulnerability has been highlighted as a key factor in ASD, and given its suggested role in social memory, the functional link between synaptic structural alterations and (social) behavioral impairments in ASD has not yet been elucidated. It is even unclear whether and how the Hippocampus, best known for its critical role in spatial navigation (e.g. “place cell” activity establishing spatial cognitive map) and episodic memory, can also process social information. Hence, we examined if and how hippocampal place cells in normal mice respond to social stimuli during different social experiments, and the extent to which place cell firing properties could be altered in Shank3(ΔC/ΔC) mice .
Our data demonstrate that hippocampal place cell activity recorded from wild-type animals could be significantly modulated by the presence of congeners in the nearby environment. While somewhat similar firing characteristics also were found in place cells recorded from Shank3(ΔC/ΔC) mice, its activity remained less susceptible to change across a multiple exposure to the social stimuli.
These data suggest that the hippocampus plays a crucial role in representing dynamically meaningful and unique experiences, associating spatial and social information, and this information processing might be altered in Shank3(ΔC/ΔC) mice (and maybe in ASD), possibly leading to cognitive inflexibility. The Shank3 gene deletion also produced significant changes in hippocampal network behavior, excitation/inhibition balance in addition to fundamental behaviors such as sleep, suggesting the importance of its physiological roles in ASD-associated phenotypes.
Keywords:
Place cell, social information, theta activity, Sharp wave-ripple, sleep, epilepsy, hippocampus, single unit recording in freely behaving mice, Shank3
Jury :
Rapporteur : M Etienne SAVE, Directeur de Recherche CNRS, Université Aix Marseille
Rapporteur : Mme Elodie EY, Chercheur Permanent, Institut Pasteur, Paris
Examinateur/Président : M Christophe MULLE : Directeur de Recherche CNRS, Université de Bordeaux
Invité : Mme Nathalie SANS : Directrice de Recherche INSERM, Université de Bordeaux