Neural circuitry underlying cortical control of vocalization-driven maternal behavior

Perception of vocalizations is critical for many species. In mammals, the central auditory pathway is highly interconnected, with corticofugal feedback projections from auditory cortex (AC) to the auditory midbrain that rival the density of feed-forward auditory input. These projections support sound localization, feature coding, and noise invariance. Because vocalizations are acoustically complex and carry social significance, we hypothesize that feedback projections from AC enable behavioral responses. Infant vocalizations that elicit parental care are highly conserved in mammals. In mice, experienced caretakers find and retrieve isolated pups into the nest when pups emit ultrasonic vocalizations (USVs). Virgin females generally don’t retrieve pups until they gain experience, for example by co-housing with a dam and litter. The onset of retrieval behavior is correlated with heightened sensitivity to USVs in left AC. To test whether corticofugal projections are required for retrieval, we chemogenetically silenced activity in left AC layer 5 (L5) – where most projections originate – during a pup retrieval assay. In experts, retrieval was greatly impaired. However, silencing a subset of L5 neurons projecting to striatum had no effect, suggesting that cortical modulation of specific projection targets may be preferentially involved in behavior. We used 2-photon calcium imaging in awake mice to compare USV responses in neurons projecting to striatum and inferior colliculus. Corticocollicular neurons in expert retrievers exhibited sustained increases in activity during USV playback compared to pure tones, while activity was equivalent during USV and tone presentation in corticostriatal neurons. This was corroborated by in vivo patch-clamp recordings in optotagged projection neurons. This sustained activity may reflect increased excitability in a network of recurrently-linked cortical and subcortical areas. To examine whether this activity develops with experience, we imaged corticocollicular neurons over co-housing. Tracking activity in corticocollicular neurons across days revealed a diversity of response profiles and changes in responsiveness to USVs.