RT Journal Article SR Electronic T1 Disrupted social memory ensembles in the ventral hippocampus underlie social amnesia in autism-associated Shank3 mutant mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.25.449869 DO 10.1101/2021.06.25.449869 A1 Kentaro Tao A1 Myung Chung A1 Akiyuki Watarai A1 Ziyan Huang A1 Mu-Yun Wang A1 Teruhiro Okuyama YR 2021 UL http://biorxiv.org/content/early/2021/06/25/2021.06.25.449869.abstract AB The ability to remember conspecifics is critical for adaptive cognitive functioning and social communication, and impairments of this ability are hallmarks of autism spectrum disorders (ASDs). Although hippocampal ventral CA1 (vCA1) neurons are known to store social memories, how their activities are coordinated remains unclear. Here we show that vCA1 social memory neurons, characterized by enhanced activity in response to memorized individuals, were preferentially reactivated during sharp-wave ripples (SPW-Rs). Spike sequences of these social replays reflected the temporal orders of neuronal activities within theta cycles during social experiences. In ASD model Shank3 knockout mice, the proportion of social memory neurons was reduced, and neuronal ensemble spike sequences during SPW-Rs were disrupted, which correlated with impaired discriminatory social behavior. These results suggest that SPW-R-mediated sequential reactivation of neuronal ensembles is a canonical mechanism for coordinating hippocampus-dependent social memories and its disruption underlies the pathophysiology of social memory defects associated with ASD.Competing Interest StatementThe authors have declared no competing interest.