An Amygdala-to-hypothalamus Circuit for Social Reward

Overview

Journal Nat Neurosci

Date 2021 Apr 6

PMID 33820999

Citations 61

Authors

Rongfeng K Hu

Yanning Zuo

Truong Ly

Jun Wang

Pratap Meera

Ye Emily Wu

Weizhe Hong

Affiliations

Soon will be listed here.

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.

Citing Articles

Fiber photometry analysis of spontaneous dopamine signals: The z-scored data are not the data.

Wallace C, Slinkard C, Shaughnessy R, Holleran K, Centanni S, Lapish C bioRxiv. 2025; .

PMID: 40060421 PMC: 11888193. DOI: 10.1101/2025.02.19.639080.

Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner.

Zhao X, Chae Y, Smith D, Chen V, DeFelipe D, Sokol J Elife. 2025; 13.

PMID: 40035330 PMC: 11879111. DOI: 10.7554/eLife.94924.

Historical loss weakens competitive behavior by remodeling ventral hippocampal dynamics.

Lai C, Chen K, Huang H, Huang X, Zhang J, Wang Y Cell Discov. 2025; 11(1):16.

PMID: 39994206 PMC: 11850767. DOI: 10.1038/s41421-024-00751-3.

Cortical and subcortical activities during food rewards versus social interaction in rats.

Rocha-Almeida F, Conde-Moro A, Fernandez-Ruiz A, Delgado-Garcia J, Gruart A Sci Rep. 2025; 15(1):4389.

PMID: 39910316 PMC: 11799384. DOI: 10.1038/s41598-025-87880-1.

The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes.

Gui Y, Zhou G, Cui S, Li H, Lu H, Zhao H Transl Psychiatry. 2025; 15(1):17.

PMID: 39843917 PMC: 11754786. DOI: 10.1038/s41398-025-03223-8.

References

Stanley D, Adolphs R . Toward a neural basis for social behavior. Neuron. 2013; 80(3):816-26. PMC: 3940487. DOI: 10.1016/j.neuron.2013.10.038. View

Chen P, Hong W . Neural Circuit Mechanisms of Social Behavior. Neuron. 2018; 98(1):16-30. PMC: 6028944. DOI: 10.1016/j.neuron.2018.02.026. View

Tamir D, Hughes B . Social Rewards: From Basic Social Building Blocks to Complex Social Behavior. Perspect Psychol Sci. 2018; 13(6):700-717. DOI: 10.1177/1745691618776263. View

Hu H . Reward and Aversion. Annu Rev Neurosci. 2016; 39:297-324. DOI: 10.1146/annurev-neuro-070815-014106. View

Chevallier C, Kohls G, Troiani V, Brodkin E, Schultz R . The social motivation theory of autism. Trends Cogn Sci. 2012; 16(4):231-9. PMC: 3329932. DOI: 10.1016/j.tics.2012.02.007. View

Nieh E, Vander Weele C, Matthews G, Presbrey K, Wichmann R, Leppla C . Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation. Neuron. 2016; 90(6):1286-1298. PMC: 4961212. DOI: 10.1016/j.neuron.2016.04.035. View

Hung L, Neuner S, Polepalli J, Beier K, Wright M, Walsh J . Gating of social reward by oxytocin in the ventral tegmental area. Science. 2017; 357(6358):1406-1411. PMC: 6214365. DOI: 10.1126/science.aan4994. View

Dolen G, Darvishzadeh A, Huang K, Malenka R . Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature. 2013; 501(7466):179-84. PMC: 4091761. DOI: 10.1038/nature12518. View

McHenry J, Otis J, Rossi M, Robinson J, Kosyk O, Miller N . Hormonal gain control of a medial preoptic area social reward circuit. Nat Neurosci. 2017; 20(3):449-458. PMC: 5735833. DOI: 10.1038/nn.4487. View

10.

Hong W, Kim D, Anderson D . Antagonistic control of social versus repetitive self-grooming behaviors by separable amygdala neuronal subsets. Cell. 2014; 158(6):1348-1361. PMC: 4167378. DOI: 10.1016/j.cell.2014.07.049. View

11.

Chen P, Hu R, Wu Y, Pan L, Huang S, Micevych P . Sexually Dimorphic Control of Parenting Behavior by the Medial Amygdala. Cell. 2019; 176(5):1206-1221.e18. PMC: 6555485. DOI: 10.1016/j.cell.2019.01.024. View

12.

Lin D, Boyle M, Dollar P, Lee H, Lein E, Perona P . Functional identification of an aggression locus in the mouse hypothalamus. Nature. 2011; 470(7333):221-6. PMC: 3075820. DOI: 10.1038/nature09736. View

13.

Wu Z, Autry A, Bergan J, Watabe-Uchida M, Dulac C . Galanin neurons in the medial preoptic area govern parental behaviour. Nature. 2014; 509(7500):325-30. PMC: 4105201. DOI: 10.1038/nature13307. View

14.

Falkner A, Grosenick L, Davidson T, Deisseroth K, Lin D . Hypothalamic control of male aggression-seeking behavior. Nat Neurosci. 2016; 19(4):596-604. PMC: 4853470. DOI: 10.1038/nn.4264. View

15.

Miller S, Marcotulli D, Shen A, Zweifel L . Divergent medial amygdala projections regulate approach-avoidance conflict behavior. Nat Neurosci. 2019; 22(4):565-575. PMC: 6446555. DOI: 10.1038/s41593-019-0337-z. View

16.

Gutzeit V, Ahuna K, Santos T, Cunningham A, Sadsad Rooney M, Munoz Zamora A . Optogenetic reactivation of prefrontal social neural ensembles mimics social buffering of fear. Neuropsychopharmacology. 2020; 45(6):1068-1077. PMC: 7162965. DOI: 10.1038/s41386-020-0631-1. View

17.

Swanson L . Cerebral hemisphere regulation of motivated behavior. Brain Res. 2000; 886(1-2):113-164. DOI: 10.1016/s0006-8993(00)02905-x. View

18.

Choi G, Dong H, Murphy A, Valenzuela D, Yancopoulos G, Swanson L . Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus. Neuron. 2005; 46(4):647-60. DOI: 10.1016/j.neuron.2005.04.011. View

19.

Li Y, Mathis A, Grewe B, Osterhout J, Ahanonu B, Schnitzer M . Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice. Cell. 2017; 171(5):1176-1190.e17. PMC: 5731476. DOI: 10.1016/j.cell.2017.10.015. View

20.

Ishii K, Osakada T, Mori H, Miyasaka N, Yoshihara Y, Miyamichi K . A Labeled-Line Neural Circuit for Pheromone-Mediated Sexual Behaviors in Mice. Neuron. 2017; 95(1):123-137.e8. DOI: 10.1016/j.neuron.2017.05.038. View