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An amygdala-to-hypothalamus circuit for social reward

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Hu, Rongfeng K., Zuo, Yanning, Ly, Truong, Wang, Jun, Meera, Pratap, Wu, Ye Emily, Hong, Weizhe·2021·Nature Neuroscience

DOI 10.1038/s41593-021-00828-2PMC PMC8236486

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Abstract

Social interactions and relationships are often rewarding, but the neural mechanisms through which social interaction drives positive experience remain poorly understood. In this study, we developed an automated operant conditioning system to measure social reward in mice and found that adult mice of both sexes display robust reinforcement of social interaction. Through cell-type-specific manipulations, we identified a crucial role for GABAergic neurons in the medial amygdala (MeA) in promoting the positive reinforcement of social interaction. Moreover, MeA GABAergic neurons mediate social reinforcement behavior through their projections to the medial preoptic area (MPOA) and promote dopamine release in the nucleus accumbens. Finally, activation of this MeA-to-MPOA circuit can robustly overcome avoidance behavior. Together, these findings establish the MeA as a key node for regulating social reward in both sexes, providing new insights into the regulation of social reward beyond the classic mesolimbic reward system.

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Authors: Hu, R. K., Zuo, Y., Ly, T., Wang, J., Meera, P., Wu, Y. E., & Hong, W.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Hong, Weizhe
ORCID: Hu, Rongfeng K.
Zuo, Yanning
Ly, Truong
Wang, Jun
Meera, Pratap
Wu, Ye Emily
Hong, Weizhe
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2021-04-05
Volume: 24
Issue: 6
Pages: 831-842
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/s41593-021-00828-2
PMC: PMC8236486
OpenAlex: W3148247179
Cited by: 174
References: 56
Citations by year: 2026: 21 · 2025: 35 · 2024: 47 · 2023: 32 · 2022: 29 · 2021: 9
FWCI: 13.57
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: UC | UCLA | David Geffen School of Medicine, University of California, Los Angeles (Marion Bowen Postdoctoral Grant)
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01NS113124)
Kinship Foundation (Searle Scholars Award)
Esther A. and Joseph Klingenstein Fund (Klingenstein-Simons Fellowship)
David and Lucile Packard Foundation (Fellowship)
McKnight Endowment Fund for Neuroscience (Scholar Award)
W. M. Keck Foundation (Junior Faculty Award)
Vallee Foundation (N/A)
Edward Mallinckrodt, Jr. Foundation (N/A)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: social reward, medial amygdala, medial preoptic area, hypothalamus, GABAergic neurons, dopamine release, nucleus accumbens, social reinforcement, avoidance behavior, sex differences, mesolimbic reward system
MeSH terms: Amygdala, Animals, Conditioning, Operant, Female, Hypothalamus, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Reinforcement, Psychology, Reward, Social Behavior, Mice, Optogenetics

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An amygdala-to-hypothalamus circuit for social reward

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