Innate sensitivity and plastic mechanisms in auditory cortex for reliable maternal behavior

Infant cries evoke powerful responses in parents1-4. To what extent are parental animals innately sensitive to neonatal vocalizations, or might instead learn about key vocal cues for appropriate parenting responses? In mice, naive virgins do not recognize the meaning of pup distress calls, but begin to retrieve pups to the nest following cohousing with a mother and litter5-8. These isolation calls can be variable, requiring co-caring virgins to generalize across features for reliable retrieval9, 10. Here, using behavioral studies combined with two-photon imaging and whole-cell recordings, we show that the onset of maternal behavior in mice results from the interaction between innate sensitivities and experience-dependent processes. We found that pup calls with inter-syllable intervals (ISIs) ranging from 75 to 375 ms elicited pup retrieval, and experienced auditory cortex generalized across these ISIs. In contrast, naive cortex was narrowly tuned to the most common or prototypical ISIs due to enhanced short-term depression of inhibitory inputs. Behavioral testing revealed that naive virgins were also more sensitive to prototypical calls than calls at other rates. Inhibitory and excitatory spiking and synaptic responses were initially mismatched in naive cortex, with untuned inhibition and overly-narrow excitation. Monitoring neuronal populations over cohousing revealed that excitatory neuronal responses broadened to represent a wide range of ISIs, while inhibitory neurons sharpened to form a perceptual boundary. Finally, we presented synthetic calls during cohousing and observed that neural and behavioral responses adjusted to match these statistics. Using inhibitory optogenetics, we found that auditory cortical activity was required to learn about specific features, whereas the oxytocinergic system was generally recruited for retrieval learning and plasticity in temporal tuning. Neuroplastic mechanisms therefore build on an innate sensitivity in the auditory cortex, enabling rapid plasticity for reliable parenting behavior.