Cornelia de Lange综合征(CdLS)是一种伴有严重认知障碍的遗传病，NIPBL基因是其常染色体显性遗传病例的致病基因，其突变导致调控基因的表达异常。然而NIPBL导致CdLS认知障碍的神经生物学机制并不清楚。通过对项目组前期建立的NIPBL基因剔除小鼠模型的研究,发现NIPBL基因剔除小鼠海马突触减少、谷氨酸NMDA受体NR2亚基表达下降，及学习记忆功能低下。谷氨酸NMDA和AMPA受体被认为与突触和长时程效应（LTP）形成和维持密切相关，是认知的结构和电生理基础。本课题拟在前期研究基础上，综合动物模型、分子生物学、电生理学和行为学等方法，通过研究NIPBL基因对突触重塑和LTP形成和NMDA受体表达和功能，及学习记忆的影响，阐明NIPBL基因在CdLS认知障碍中的作用和可能机制。这有助于了解NIPBL基因的神经生物学功能及CdLS发病机制，为其诊疗提供新策略。

Cornelia de Lange syndrome (CdLS) is a genetic disease with severe cognitive impairment. The mutation in the NIPBL gene is the cause of CdLS in autosomal dominant patients, which leads to an abnormal gene expression. However, the neurobiological mechanism of NIPBL is still unclear. In a NIPBL gene knockout mouse model established in our previous study, we found decreased expressions of synapses and NR2 subunit of the N-methyl-D-aspartate (NMDA) receptor, and lowered in learning and memory abilities. NMDA and alpha-amino-3-hydroxy-5-methyl-4-oxazole propionic acid (AMPA) receptors of glutamate considered to play an crucial role in the formation and maintnance of synapses and long-term potentiation (LTP), which is the structural and electrophysiological basis of cognitive function. Herein, we plan to clarify the effects and mechanisms of NIPBL gene on cognitive impairment in CdLS by investigating the role of the NIPBL gene on synaptic remodeling, LTP formation, as well as NMDA receptors expression and function using animal models, molecular biology, electrophysiology, and behavioral methods. It will help us to understand the neurobiological function of the NIPBL gene and the CdLS pathogenesis, also provides new insights into the diagnosis and intervention of CdLS.