PV（parvalbumin）神经元的发育与分化异常致力于自闭症的发生。我们前期研究发现LXRβ缺失导致小鼠神经精神异常，在LPS注射后引起类似于自闭症样的行为，并伴有大脑皮层内PV神经元数量显著减少，提示LXRβ缺失可能通过抑制PV神经元的发育而参与自闭症形成。然而LXRβ调控大脑皮层内PV神经元发育的途径与机制目前仍不明确。本课题将LXRβ敲除小鼠与GAD67-GFP基因敲入小鼠进行杂交，同时结合胚胎电转、MGE移植、膜片钳记录，检测LXRβ调控大脑皮层内PV神经元发育、分化及成熟的途径；采用染色质沉淀技术（ChIP）检测LXRβ-Sp1复合体对PV神经元发育关键转录因子Nkx2.1转录的动态调节，明确与启动子结合的区域。阐明LXRβ缺失通过抑制皮层内PV神经元发育参与自闭症样行为发生的分子机制，为自闭症的预防与治疗提供新线索。

Abnormal development and differentiation of parvalbumin(PV) neuron is considered to be a key factor related to pathogenesis of autism. Our previous study found that LXRβ deletion in mouse resulted in neuropsychiatric disorders. Autism-like behavior was induced by LPS injection and PV neurons in cerebral cortex were decreased significantly, suggesting that LXRβ might be involved in autism pathogenesis through inhibition of PV neuronal development . However , the modulating pathway and mechanism of LXRβ in the development of PV neurons of cerebral cortex have not been well explored. In the present study,The roles of LXRβ in the development ,differentiation, and maturation of PV neurons of cerebral cortex will be investigated with LXRβ knockout and GAD67-GFP knockin mice , and combination with embryonic electroporation, MGE transplantation, and patch clamp recording. A chromatin precipitation will be used to detect dynamic modulation of NKx2.1 by LXRβ-Sp1transcription complex, and analyze binding region on the promoter. It will clarify the underlying mechanism of LXRβ deletion involved in the occurrence of autistic like behaviors through abnormal development of PV neurons, to provide new clues for the prevention and treatment of autism.