ETD

• social behavior

Social interaction is a fundamental biological need: acute social isolation induces a robust rebound in social behavior in rodents, suggesting that social drive is regulated in a homeostatic manner. Two genetically defined neuronal populations in the medial preoptic nucleus (MPN) of the hypothalamus bidirectionally regulate social homeostasis: excitatory Mc4r+/Vglut2+ neurons activated during isolation and inhibitory Trhr+/Vgat+ neurons activated during reunion. Strikingly, the magnitude of social rebound varies across biological variables. FVB/NJ mice display strong rebound behavior, whereas C57BL/6J mice show lower responses. Moreover, females show more robust social rebound than males. These behavioral differences are not simply explained by differences in cell number, but rather by differences in neuronal activity and circuit engagement. This natural variation provides a robust model to dissect the molecular and circuit mechanisms underlying social homeostasis. By integrating circuit mapping and functional imaging, this work aims to determine whether sex- and strain-dependent differences in social drive arise from altered connectivity, intrinsic neuronal activity, or a combination of both. Understanding the anatomical and physiological organization of the MPN circuits underlying the response to social isolation will advance our knowledge of how social need is encoded in the hypothalamus and provide insight into the biological basis of natural variation in social behavior.