Age-specific regulation of sociability by hypothalamic Agrp neurons

Social isolation enhances sociability, suggesting that social behavior is maintained through a homeostatic mechanism. Further, mammalian social needs shift dramatically from infancy through adolescence into adulthood, raising the question of whether the neural mechanisms governing this homeostatic regulation evolve across developmental stages. Here, we show that agouti-related peptide (Agrp) neurons in the arcuate nucleus of the hypothalamus, which are known to drive hunger in adults, are activated by social isolation from weaning through adolescence but not in adulthood. Importantly, the activity of these neurons is critical for social behavior during adolescence: inhibiting Agrp neurons reduced isolation-induced sociability in juveniles, but not in adults, and Agrp neuron activation promoted sociability only in young mice. After isolation, reunion with siblings or other conspecifics, but not unfamiliar adult males or amicable rat pups, rapidly decreased neuronal activity in juveniles, an effect requiring intact olfaction. These findings identify Agrp neurons as a key component of the circuitry governing age-specific social homeostasis.