<i>Auts2</i> deletion involves in DG hypoplasia and social recognition deficit: The developmental and neural circuit mechanisms
Jun Li, Xiaoxuan Sun, Yang You, Qiongwei Li, Chengwen Wei, Linnan Zhao, Mengwen Sun, Hu Meng, Tian Zhang, Weihua Yue, Lifang Wang, Dai Zhang
Abstract
The involvement of genetic risk and the underlying developmental and neural circuit mechanisms in autism-related social deficit are largely unclear. Here, we report that deletion of AUTS2 , a high-susceptibility gene of ASDs, caused postnatal dentate gyrus (DG) hypoplasia, which was closely relevant to social recognition deficit. Furthermore, a previously unknown mechanism for neural cell migration in postnatal DG development was identified, in which Auts2-related signaling played a vital role as the transcription repressor. Moreover, the supramammillary nucleus (SuM)–DG-CA3 neural circuit was found to be involved in social recognition and affected in Auts2 -deleted mice due to DG hypoplasia. Correction of DG-CA3 synaptic transmission by using a pharmacological approach or chemo/optogenetic activation of the SuM-DG circuit restored the social recognition deficit in Auts2 -deleted mice. Our findings demonstrated the vital role of Auts2 in postnatal DG development, and this role was critical for SuM-DG-CA3 neural circuit-mediated social recognition behavior.