记忆缺失是老年痴呆疾病早期最常见临床症状，与海马突触环路变性损伤密切相关。由于研究技术手段限制，迄今，我们对海马环路的结构，功能，及其在老年痴呆记忆缺失发生与发展进程中的作用仍不清楚。本项目的关键科学问题如下：.1)海马环路内有哪些神经细胞建立了单突触联接，这些单突触联接的功能（如时间与空间记忆、记忆存储与提取等）是什么？.2)环路内哪些神经突触在老年痴呆疾病记忆丢失过程中发生变性损伤？.3)阻止或逆转海马环路神经突触变性损伤能否有效防治老年痴呆记忆丢失？.本项目将应用我们已经建立的光遗传，单突触示踪和动态脑功能记录技术，结合老年痴呆疾病基因突变动物模型，阐明以上三个关键科学问题，确立海马突触环路变性损伤在老年痴呆疾病记忆丢失发生与发展过程中的作用，从而建立老年痴呆疾病诊疗的新方法和新手段。

A loss of memory is one of the earliest clinical signs in Alzheimer’s disease and is closely associated with a degeneration of synaptic circuits in the hippocampus. Due to technique limitations, little is known about the structure and function of the individual synaptic circuits in the hippocampus and how synaptic affects in the hippocampus affect the progression of Alzheimer’s disease. The followings are the key questions:.1..The hippocampus contains over 300 million of neurons, which of these neurons develop monosynaptic connections? what are the roles of these connections?.2..Which of these synaptic connections in the hippocampus are affected in Alzheimer’s disease?.3..Whether interception of synaptic degeneration in the hippocampus rescues a memory loss in Alzheimer’s disease?.The main goal of this project is to address these three key questions and determine that a selective degeneration of synaptic circuits in the hippocampus contributes to the progression of memory loss in Alzheimer’s disease, and hence provides new strategies and new techniques for the disease therapy.