Mitofusin-2 in nucleus accumbens D2-MSNs regulates social dominance and neuronal function.

Cell reports 2023 Jul 25

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The nucleus accumbens (NAc) is a brain hub regulating motivated behaviors, including social competitiveness. Mitochondrial function in the NAc links anxiety with social competitiveness, and the mitochondrial fusion protein mitofusin 2 (Mfn2) in NAc neurons regulates anxiety-related behaviors. However, it remains unexplored whether accumbal Mfn2 levels also affect social behavior and whether Mfn2 actions in the emotional and social domain are driven by distinct cell types. Here, we found that subordinate-prone highly anxious rats show decreased accumbal Mfn2 levels and that Mfn2 overexpression promotes dominant behavior. In mice, selective Mfn2 downregulation in NAc dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) induced social subordination, accompanied by decreased accumbal mitochondrial functions and decreased excitability in D2-MSNs. Instead, D1-MSN-targeted Mfn2 downregulation affected competitive ability only transiently and likely because of an increase in anxiety-like behaviors. Our results assign dissociable cell-type specific roles to Mfn2 in the NAc in modulating social dominance and anxiety. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Sriparna Ghosal, Elias Gebara, Eva Ramos-Fernández, Alessandro Chioino, Jocelyn Grosse, Isabelle Guillot de Suduiraut, Olivia Zanoletti, Bernard Schneider, Antonio Zorzano, Simone Astori, Carmen Sandi. Mitofusin-2 in nucleus accumbens D2-MSNs regulates social dominance and neuronal function. Cell reports. 2023 Jul 25;42(7):112776