神经细胞的PDZ蛋白作为一大类细胞脚手架蛋白，能够和膜上受体结合，传递细胞内信号，精细调节细胞的结构和功能，促进整个神经环路的发育和各个核团功能的整合，是维持稳定的大脑神经环路结构和功能的分子基础。我们前期初步研究发现，位于海马CA3区特异性表达的PDZ蛋白Lnx1与膜上EphB受体相结合，并与其他PDZ结合蛋白如NMDA受体一起参与调控海马区神经环路的形成。然而，有关Lnx1在发育期和成年脑中的主要生理作用和具体分子机制尚不清楚。因此，本课题计划以Lnx1基因敲除小鼠模型为基础，阐明Lnx1信号在海马神经连接和环路功能中的调节规律，探讨发育期先天性行为的形成和成年期习得性行为模式中突触可塑性的调节机制。本研究将有助于认识PDZ蛋白在神经生理和病理过程中环路构建的新机制，为认知神经疾病的治疗策略提供新的思路。

As a large group of scaffold proteins, PDZ（PSD-95-discs large-zona occludens-1） proteins transduce intracellular signaling, upon binding with membrane receptors, to regulate neuron structure and function precisely, and promote integration of circuits development and inter-nuclei function. In the primarily study, we identify Lnx1, a PDZ protein specifically expressed in hippocampal CA3 region, that bind EphB receptor to transduce signals, accompanied with other PDZ binding proteins such as NMDA receptor, to regulate formation of neural circuits. However, the major physiological role and molecular mechanism of Lnx1 in vivo in the developing and adult brain remains poorly understood. Therefore, the proposed studies aim to clarify the role of Lnx1 for nerve wiring and circuits function in hippocampus, using Lnx1 knockout mice, to investigate the mechanism of innate behavior generation during developmental period and synaptic plasticity for learned behavior in adulthood. The study should lead to an increased understanding of new mechanism of Lnx1 for circuits formation in neural physiology and pathology, which helps bring novel therapeutic methods for cognitive brain disorders.