A dedicated hypothalamic oxytocin circuit controls aversive social learning

Takuya Osakada (), Rongzhen Yan, Yiwen Jiang, Dongyu Wei, Rina Tabuchi, Bing Dai, Xiaohan Wang, Gavin Zhao, Clara Xi Wang, Jing-Jing Liu, Richard W. Tsien, Adam C. Mar and Dayu Lin ()
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Takuya Osakada: New York University Langone Medical Center
Rongzhen Yan: New York University Langone Medical Center
Yiwen Jiang: New York University Langone Medical Center
Dongyu Wei: New York University Langone Medical Center
Rina Tabuchi: New York University Langone Medical Center
Bing Dai: New York University Langone Medical Center
Xiaohan Wang: New York University Langone Medical Center
Gavin Zhao: New York University Langone Medical Center
Clara Xi Wang: New York University Langone Medical Center
Jing-Jing Liu: New York University Langone Medical Center
Richard W. Tsien: New York University Langone Medical Center
Adam C. Mar: New York University Langone Medical Center
Dayu Lin: New York University Langone Medical Center

Nature, 2024, vol. 626, issue 7998, 347-356

Abstract: Abstract To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.

Date: 2024
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DOI: 10.1038/s41586-023-06958-w

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