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 dams 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.