Asic3 ^-/- female mice with hearing deficit affects social development of pups

Background: Infant crying is an important cue for mothers to respond adequately. Inappropriate response to infant crying can hinder social development in infants. In rodents, the pup-mother interaction largely depends on pup's calls. Mouse pups emit high frequency to ultrasonic vocalization (2-90 kHz) to communicate with their dam for maternal care. However, little is known about how the maternal response to infant crying or pup calls affects social development over the long term. Methodology/Principal Findings: Here we used mice lacking acid-sensing ion channel 3 (Asic3^-/-) to create a hearing deficit to probe the effect of caregiver hearing on maternal care and adolescent social development. Female Asic3^-/- mice showed elevated hearing thresholds for low to ultrasonic frequency (4-32 kHz) on auditory brain stem response, which thus hindered their response to their pups' wriggling calls and ultrasonic vocalization, as well as their retrieval of pups. In adolescence, pups reared by Asic3^-/- mice showed a social deficit in juvenile social behaviors as compared with those reared by wild-type or heterozygous dams. The social-deficit phenotype in juvenile mice reared by Asic3^-/- mice was associated with the reduced serotonin transmission of the brain. However, Asic3^-/- pups cross-fostered to wild-type dam showed rescued social deficit. Conclusions/Significance: Inadequate response to pups' calls as a result of ASIC3-dependent hearing loss confers maternal deficits in caregivers and social development deficits in their young.