A hypothalamic circuit underlying dynamic control of instinctive social need

Social interaction is a fundamental and evolutionarily conserved need. Social grouping decreases the risk of predation, reduces energy consumption and leads to mutually beneficial behaviors such as parenting and group foraging. By contrast, social isolation leads to a range of mental and physical problems in both human and animals. However, how the brain controls instinctive social need and what neuronal populations and circuits are involved, remain unknown.

In this study, we report the identification of novel populations of hypothalamic neurons in the medial preoptic nucleus (MPN) in mice that are activated by either social isolation (MPN-isolation neurons) or social reunion (MPN-reunion neurons) and form a unique local excitation-inhibition microcircuit regulating a dynamic balance between social seeking and social satiety. Using micro-endoscopic Ca2+ imaging in freely behaving animals, we uncovered the sustained activation of MPN-isolation neurons during social isolation and their persistent inhibition during social reunion, therefore serving as a social state indicator. Using functional circuit mapping approaches, we found that local GABAergic neurons that are activated by social interaction have direct inhibitory input onto MPN-isolation neurons and thus likely provide social satiety signal. The functional contributions of these neurons to social need were causally assessed by optogenetic approaches. Moreover, cell type-specific viral-mediated neural tracing uncovered the connectivity between these neuronal populations and brain areas associated with emotional state, social reward as well as metabolism, offering an overarching understanding of the brain regulation of social need. Finally, we have identified social touch as an important sensory input modulating social need and social satiety.

By monitoring population activity, manipulating cell-type specific neuronal activity and mapping brain-wide connectivity, this study uncovers local and global circuit mechanisms underlying social homeostasis.