Shank3 deficits in the anteromedial bed nucleus of the stria terminalis trigger an anxiety phenotype in mice

Author:

Contestabile Alessandro12ORCID,Casarotto Giulia1,Musardo Stefano1,Espinosa Pedro1,Maltese Federica1,Jiang Yong‐hui3,Bellone Camilla1ORCID,Glangetas Christelle14ORCID

Affiliation:

1. Department of Basic Neuroscience University of Geneva Geneva Switzerland

2. Department of Neuroscience Karolinska Institutet, Biomedicum Stockholm Sweden

3. Department of Genetics Yale University School of Medicine New Haven Connecticut USA

4. University Bordeaux, CNRS, IMN, UMR 5293 Bordeaux France

Abstract

AbstractAnxiety disorders are the most prevalent co‐morbidity factor associated with the core domains of autism spectrum disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co‐occurrence of ASD and anxiety disorders are still poorly explored. One of the key questions that remained unsolved is the role of Shank3 protein in anxiety behaviours. Firstly, we characterize the developmental trajectories of locomotor, social behaviour and anxiety traits in a mouse model of ASD. We highlight that the anxiety phenotype is a late‐onset emerging phenotype in mice with a Shank3Δe4‐22 mutation. Consequently, we used an shRNA strategy to model Shank3 insufficiency in the bed nucleus of the stria terminalis (BNST), a brain region exerting a powerful control on anxiety level. We found that Shank3 downregulation in the anteromedial BNST (amBNST) induced anxiogenic effects and enhanced social avoidance after aversive social defeat. Associated with these behavioural defects, we showed alteration of glutamatergic synaptic functions in the amBNST induced by Shank3 insufficiency during adolescence. Our data strongly support the role of Shank3 in the maturation of amBNST, and its key role in anxiety control. Our results may further help to pave the road on a better understanding of the neuronal mechanisms underlying anxiety disorders implicated in ASDs.

Funder

Fondation Pierre Mercier

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Fondation pour la Recherche Médicale

Publisher

Wiley

Subject

General Neuroscience

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