Maternal experience alters brain-wide representation of infant cries.

Pup calls signal the presence of a mouse infant in need of care (Bernd Haack et al., 1983; Ehret, 2005). Previous work demonstrated that experience-dependent plasticity within the left primary auditory cortex is oxytocin-facilitated and enhances neural and behavioral responses to these distress vocalizations (Marlin et al., 2015). However, whether maternal experience reshapes pup call processing beyond auditory regions remains unknown. Here, we show that both innate and learned maternal experience shape pup call-evoked behavior and brain-wide neural responses. Combining behavioral assays, whole-brain activity mapping, and oxytocinergic projection analyses, we find that pup calls recruit distinct large-scale neural networks in naïve virgins, experienced virgins, and mothers. With more maternal experience we observe a distributed pup call response network that is sparser yet more strongly coactivated, consistent with a more efficient and specialized neural representation of infant cues. We identified an oxytocin-dense circuit that shows an experience-dependent pup call response pattern. Therefore, we propose that experience-dependent refinement of the brain-wide response to pup calls is facilitated by oxytocin. Taken together, our findings reveal that maternal experience refines brain-wide sensory processing to support adaptive caregiving behavior.