摘要
Abnormal synchronous neuronal activity has been widely detected by brain imaging of autistic patients,but its underlying neural mechanism remains unclear.Compared with wild-type mice,our in vivo two-photon imaging showed that transgenic(Tgl)mice over-expressing human autism risk gene MeCP2 exhibited higher neuronal synchrony in the young but lower synchrony in the adult stage.Whole-cell recording of neuronal pairs in brain slices revealed that higher neuronal synchrony in young postnatal Tgl mice was atributed mainly to more prevalent giant slow inward currents(SICs).Both in vivo and slice imaging further demonstrated more dynamic activity and higher synchrony in astrocytes from young Tgl mice.Blocking astrocytic gap junctions markedly decreased the generation of SICs and overall cell synchrony in the Tgl brain.Furthermore,the expression level of Cx43 protein and the coupling efficiency of astrocyte gap junctions remained unchanged in Tgi mice.Thus,astrocytic gap junctions facilitate but do not act as a direct trigger for the abnormal neuronal synchrony in young Tgl mice,revealing the potential role of the astrocyte network in the pathogenesis of MeCP2 duplication syndrome.
基金
supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100)
a National Natural Science Foundation of China project(31671113)
a Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)
and the State Key Laboratory of Neuroscience.
