A hypothalamic circuit underlying the dynamic control of social homeostasis

Ding Liu, Mostafizur Rahman, Autumn Johnson, Ryunosuke Amo, Iku Tsutsui-Kimura, Zuri A. Sullivan, Nicolai Pena, Mustafa Talay, Brandon L. Logeman, Samantha Finkbeiner, Lechen Qian, Seungwon Choi, Athena Capo-Battaglia, Ishmail Abdus-Saboor, David D. Ginty, Naoshige Uchida, Mitsuko Watabe-Uchida and Catherine Dulac ()
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Ding Liu: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Mostafizur Rahman: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Autumn Johnson: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Ryunosuke Amo: Center for Brain Science, Harvard University
Iku Tsutsui-Kimura: Center for Brain Science, Harvard University
Zuri A. Sullivan: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Nicolai Pena: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Mustafa Talay: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Brandon L. Logeman: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Samantha Finkbeiner: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Lechen Qian: Center for Brain Science, Harvard University
Seungwon Choi: Howard Hughes Medical Institute, Harvard Medical School
Athena Capo-Battaglia: Howard Hughes Medical Institute, Center for Brain Science, Harvard University
Ishmail Abdus-Saboor: Zuckerman Mind Brain Behavior Institute, Columbia University
David D. Ginty: Howard Hughes Medical Institute, Harvard Medical School
Naoshige Uchida: Center for Brain Science, Harvard University
Mitsuko Watabe-Uchida: Center for Brain Science, Harvard University
Catherine Dulac: Howard Hughes Medical Institute, Center for Brain Science, Harvard University

Nature, 2025, vol. 640, issue 8060, 1000-1010

Abstract: Abstract Social grouping increases survival in many species, including humans1,2. By contrast, social isolation generates an aversive state (‘loneliness’) that motivates social seeking and heightens social interaction upon reunion3–5. The observed rebound in social interaction triggered by isolation suggests a homeostatic process underlying the control of social need, similar to physiological drives such as hunger, thirst or sleep3,6. In this study, we assessed social responses in several mouse strains, among which FVB/NJ mice emerged as highly, and C57BL/6J mice as moderately, sensitive to social isolation. Using both strains, we uncovered two previously uncharacterized neuronal populations in the hypothalamic preoptic nucleus that are activated during either social isolation or social rebound and orchestrate the behaviour display of social need and social satiety, respectively. We identified direct connectivity between these two populations and with brain areas associated with social behaviour, emotional state, reward and physiological needs and showed that mice require touch to assess the presence of others and fulfil their social need. These data show a brain-wide neural system underlying social homeostasis and provide significant mechanistic insights into the nature and function of circuits controlling instinctive social need and for the understanding of healthy and diseased brain states associated with social context.

Date: 2025
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DOI: 10.1038/s41586-025-08617-8

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