TY - JOUR T1 - Deconstruction of the retrosplenial granular cortex for social behavior in the mouse model of fragile X syndrome JF - bioRxiv DO - 10.1101/2021.01.24.428008 SP - 2021.01.24.428008 AU - Hui-Fang Shang AU - Ruonan Cai AU - Hao Sun AU - Tao Sheng AU - Yan-Na Lian AU - Li Liu AU - Wei Chen AU - Lixia Gao AU - Han Xu AU - Chen Zhang AU - Jian-Hong Luo AU - Xinjian Li AU - Xiang-Yao Li Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/26/2021.01.24.428008.abstract N2 - Deficits in fragile X mental retardation 1 protein lead to fragile X syndrome (FXS) with mental retardation and social activity disorder. Until now, the neuronal circuits that mediate the social impairments of FXS were mostly unclear. Accidently, we found fewer c-fos expression in RSG of KO than WT mice after social behavior test. Inactivation of RSG neurons decreased social novelty but not the sociability of naive mice. Interestingly, although the RSG neurons of KO mice had higher background activity, fewer social contact-related Ca2+ neurons were observed during social interaction test via one-photon Ca2+ imaging in freely-behaving mice. Strikingly, enhancing the activity of RSG neurons rescued the abnormal social novelty in KO mice. Further studies proved that the innervations from the subiculum and ACC to RSG contributes to the social behavior. Take together, we found that abnormal activity in the retrosplenial granular cortex (RSG) led to social novelty deficits in Fmr1-knockout (KO) mice. Moreover, selective manipulation of RSG neurons may be an effective strategy to treat the social deficits in FXS.One Sentence Summary Deletion of FMRP leads to lower social-related neuronal activity in the RSG; this causes social novelty deficits in Fmr1-KO mice.Competing Interest StatementThe authors have declared no competing interest. ER -