突触稳态可塑性（HSP）对维持神经元和神经回路稳定性至关重要。研究其调控机制对探索包括自闭症和阿尔茨海默氏病在内的多种神经性疾病的发生有重要意义。HSP形成的调控机制在很大程度上是未知的。改变AMPA受体（AMPAR）在突触后膜上的分子组成和表达水平是形成HSP的主要手段。申请者发现5-焦磷酸-五磷酸肌醇（5-IP7）调控AMPAR在突触中的组成和水平并影响在HSP中起重要作用的PI（3，4，5）P3信号通路，同时突触活动强度双向调节5-IP7的合成酶IP6K1在突触中的表达，提示5-IP7/IP6K1在突触传递和HSP中的重要作用。本课题拟阐明5-IP7/IP6K1对突触后AMPAR组成和水平以及突触传递功能的影响，并解析5-IP7在体内和体外对HSP形成的调控作用及其分子机制。预期成果将揭示一种调控突触传递和HSP形成的崭新机制，也为由HSP形成异常引起的神经性疾病提供新的治疗靶标。

Homeostatic synaptic plasticity (HSP) is crucial in maintaining the cellular and network stability and response capability. Accumulating evidence has revealed exciting new links between homeostatic synaptic plasticity and a variety of neurological and psychiatric diseases including autism and Alzheimer's disease. However, its underlying mechanisms are largely unknown. HSP can be regulated at the postsynaptic side by altering the types and level of AMPAR. We found that 5-diphosphoinositol pentakisphosphate (5-IP7) regulated not only the expression of AMPAR at synapse but also PI(3,4,5)P3 signaling pathway which played an important role in HSP. In addition, the synaptic expression of IP6K1 was bidirectionally regulated by synaptic activity. This study will systematically dissect the role and mechanism of 5-IP7/IP6K1 in the regulation of synaptic transmission and HSP. The expected results will provide not only a fresh piece of insight into the signaling pathways regulating homeostatic synaptic plasticity but also identify novel therapeutic targets for treatment of neurological and psychiatric diseases.