Hypothalamic plasticity for alloparenting in male mice

Abstract

Repeated exposure to young can induce caregiving in virgin female mice, a phenomenon known as pup sensitization, but whether virgin males can similarly acquire parental behavior and the neural mechanisms underlying this transition remain unclear. We show that 7 days of continuous pup exposure reliably converts virgin adult male mice to a parental state. This transition requires calcitonin receptor (CalcR)-expressing neurons in the medial preoptic area (MPOA): silencing MPOACalcR neurons disrupts both the acquisition and expression of paternal behavior, whereas optogenetic activation of GABAergic MPOACalcR neurons promotes caregiving in virgin males. Longitudinal two-photon calcium imaging reveals that MPOACalcR neurons develop enhanced pup-selective responses as males transition to a parental state. Moreover, CalcR signaling in the MPOA promotes synaptic potentiation and facilitates the emergence of parental behavior. These results identify an experience-dependent hypothalamic plasticity mechanism that enables parental behavior in non-father males.