Brain circuits that regulate social behavior

Abstract

Social interactions are essential for the survival of individuals and the reproduction of populations. Social stressors, such as social defeat and isolation, can lead to emotional disorders and cognitive impairments. Furthermore, dysfunctional social behaviors are hallmark symptoms of various neuropsychiatric disorders, including autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). Consequently, understanding the neural circuit mechanisms underlying social behaviors has become a major focus in neuroscience. Social behaviors, which encompass a wide range of expressions and phases, are regulated by complex neural networks. In this review, we summarize recent progress in identifying the circuits involved in different types of social behaviors, including general social investigation, social preference, mating, aggression, parenting, prosocial behaviors, and dominance behaviors. We also outline the circuit mechanisms associated with social deficits in neuropsychiatric disorders, such as ASD, schizophrenia, and PTSD. Given the pivotal role of rodents in social behavior research, our review primarily focuses on neural circuits in these animals. Finally, we propose future research directions, including the development of specific behavioral paradigms, the identification of circuits involved in motor output, the integration of activity, transcriptome, and connectome data, the multifunctional roles of neurons with multiple targets, and the interactions among multiple brain regions.

Fig. 1. The generation and circuit mechanism of general social preference.

A Schematics of the social preference test. B Schematic illustrating the generation of social preference. C Representative neural circuits underlying sociability. D Representative neural circuits underlying social novelty preference. BF basal forebrain, BLA basolateral amygdala, CeA central amygdala, CPu caudate putamen, HPC hippocampus, IL infralimbic cortex, IPN interpeduncular nucleus, LDTg lateral dorsal tegmentum, LEC lateral entorhinal cortical, LS lateral septum, MiTg microcellular tegmentum, mPFC medial prefrontal cortex, MS medial septum, NAc nucleus accumbens, PrL prelimbic cortex, PVN hypothalamic paraventricular nucleus, PVT paraventricular thalamus, Re thalamic nucleus reuniens, RSA retrosplenial agranular cortex, SuM hypothalamic supramammillary nucleus, VMT ventromedial thalamus, VTA ventral tegmental area.

Fig. 2. Circuits regulating innate social behaviors.

A–D Representative brain regions, molecules, and circuits involved in A male copulation, B female copulation, C aggression, and D parenting. Dotted lines represent behavior-related circuits that have not yet been validated using advanced manipulation techniques. Molecular markers are indicated within the corresponding circles of brain regions. If a circuit terminates inside a circle, it has been confirmed to originate from or target a specific neuronal population within that region. If a circuit terminates outside a circle, it has been confirmed to involve the region, but the specific neuronal population remains unidentified. For example, in Fig. 2A, MPOA^Esr1/Vgat neurons project to VMHvl to promote male copulation; however, it remains unclear whether this circuit targets VMHvl^Esr1 neurons. AC auditory cortex, ACC anterior cingulate cortex, AOB accessory olfactory bulb, ARH arcuate nucleus of the hypothalamus, AVPV. anteroventral periventricular nucleus, BF basal forebrain, BNST bed nucleus of the stria terminalis, COApm posteromedial cortical amygdala, dCA2 dorsal CA2, dLS dorsolateral septum, DRN dorsal raphe nucleus, LC locus coeruleus, LH lateral hypothalamus, LHb lateral habenula, MeA medial amygdala, mPFC medial prefrontal cortex, MPOA medial preoptic area, NAc nucleus accumbens, PA posterior amygdala, PAG periaqueductal gray, PIL posterior intralaminar nucleus of the thalamus, PMv ventral premammillary nucleus, pSI posterior substantia innominate, PVN hypothalamic paraventricular nucleus, SCN suprachiasmatic nucleus, SPZ subparaventricular zone, sSC medial superficial layers of ipsilateral superior colliculus, SuM hypothalamic supramammillary nucleus, vHPC ventral hippocampus, vLS ventrolateral septum, VMH ventromedial hypothalamus, VMHc central VMH, VMHd dorsal VMH, VMHvl ventrolateral VMH, VNO vomeronasal organ, VTA ventral tegmental area.

Fig. 3. Neural mechanisms underlying winning-dependent aggression enhancement.

This figure is modified from [107]. VMHvl the ventrolateral part of the ventromedial hypothalamus.

Fig. 4. Circuits regulating empathy and social hierarchy.

A ACC-centered circuits involved in empathy. Dotted lines represent circuits that have not yet been validated using manipulation-based techniques. B mPFC-centered circuits involved in the establishment of social hierarchy. ACC anterior cingulate cortex, BLA basolateral amygdala, dmPFC dorsomedial prefrontal cortex, DRN dorsal raphe nucleus, IC insular cortex, LA lateral part of basolateral amygdala, LH lateral hypothalamus, LHb lateral habenula, LS lateral septum, MeA medial amygdala, MDT mediodorsal thalamus, NAc nucleus accumbens, PAG periaqueductal gray, VTA ventral tegmental area.

Fig. 5. Circuits mediating social deficit in autism.

BLA basolateral amygdala, BNST bed nucleus of the stria terminalis, CPu caudate putamen, CN cerebellar nuclei, DG dentate gyrus, LH lateral hypothalamus, LS lateral septum, mPFC medial prefrontal cortex, MS medial septum, NAc nucleus accumbens, nRT thalamic reticular nucleus, VB ventrobasal thalamus, VMT ventromedial thalamus, VTA ventral tegmental area, ZI zona incerta.