The brains of prospective parents undergo profound changes believed to support infant caregiving, which is crucial for offspring survival. Recent studies show that parental plasticity extends to cortical regions, affecting both early sensory processing and higher brain functions. While significant progress has been made in understanding motherhood-induced plasticity, much less is known about analogous changes in the paternal brain. Indeed, the extent to which paternal and maternal plasticity mirror each other remains unclear. Here, we tracked neuronal responses in the primary auditory cortex (ACx) of male mice using longitudinal two-photon calcium imaging before, during, and after fatherhood. Behaviorally, male mice transitioned from aggressive, self-oriented behaviors to transient displays of nurturing and parental care. Neurons in the ACx of fathers exhibited enhanced and accelerated discriminability of pup vocalizations. In parallel, slice electrophysiology revealed increased neuronal excitability associated with fatherhood. Mechanistically, we identified a role for prolactin in cortical plasticity. Prolactin signaling was elevated in the ACx of fathers, and experimental manipulation of prolactin levels selectively altered improvement in neuronal discriminability. Together, these findings reveal a novel mechanism underlying paternal plasticity, which is distinct from its maternal counterpart. Our findings offer mechanistic insight into how neuroendocrine signaling shapes sensory plasticity that supports parental caregiving.

Supervisor: Prof. Adi Mizrahi