SWI/SNF chromatin remodeler complex within the reward pathway is required for behavioral adaptations to stress

Abdallah Zayed, Camille Baranowski, Anne-Claire Compagnion, Cécile Vernochet, Samah Karaki, Romain Durand- de Cuttoli, Estefani Saint-Jour, Soumee Bhattacharya, Fabio Marti, Peter Vanhoutte, Moshe Yaniv, Philippe Faure, Jacques Barik, Laurence Amar, François Tronche () and Sébastien Parnaudeau
Additional contact information
Abdallah Zayed: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Camille Baranowski: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Anne-Claire Compagnion: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Cécile Vernochet: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Samah Karaki: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Romain Durand- de Cuttoli: Sorbonne Université, Neurophysiology and Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM, UPMC
Estefani Saint-Jour: Sorbonne Université, Neuronal Signaling and Gene Regulation, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM, UPMC
Soumee Bhattacharya: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Fabio Marti: Sorbonne Université, Neurophysiology and Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM, UPMC
Peter Vanhoutte: Sorbonne Université, Neuronal Signaling and Gene Regulation, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM, UPMC
Moshe Yaniv: Pasteur Institute
Philippe Faure: Sorbonne Université, Neurophysiology and Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM, UPMC
Jacques Barik: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Laurence Amar: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
François Tronche: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM
Sébastien Parnaudeau: Sorbonne Université, Gene Regulation and Adaptive Behaviors, Neuroscience Paris-Seine, IBPS. CNRS UMR8246, INSERM

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Enduring behavioral changes upon stress exposure involve changes in gene expression sustained by epigenetic modifications in brain circuits, including the mesocorticolimbic pathway. Brahma (BRM) and Brahma Related Gene 1 (BRG1) are ATPase subunits of the SWI/SNF complexes involved in chromatin remodeling, a process essential to enduring plastic changes in gene expression. Here, we show that in mice, social defeat induces changes in BRG1 nuclear distribution. The inactivation of the Brg1/Smarca4 gene within dopamine-innervated regions or the constitutive inactivation of the Brm/Smarca2 gene leads to resilience to repeated social defeat and decreases the behavioral responses to cocaine without impacting midbrain dopamine neurons activity. Within striatal medium spiny neurons, Brg1 gene inactivation reduces the expression of stress- and cocaine-induced immediate early genes, increases levels of heterochromatin and at a global scale decreases chromatin accessibility. Altogether these data demonstrate the pivotal function of SWI/SNF complexes in behavioral and transcriptional adaptations to salient environmental challenges.

Date: 2022
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DOI: 10.1038/s41467-022-29380-8

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