记忆缺失是阿尔茨海默病中（Alzheimer’s disease，AD）最常见的临床症状之一，其与海马突触环路退化密切相关，但涉及的具体神经环路仍未完全阐明，特别是调制海马信息输入的神经环路和记忆缺失之间的关联还不清楚。研究证实乳头体上核（supramammillary，SUM）调制DG中Theta振荡，增加DG的突触输入。预实验发现SUM中新环路SUMlPV-dDGPV对海马背侧DG投射强烈，并且在AD模型小鼠中该环路可能损伤。所以，本项目拟在此基础上，运用AD模型小鼠，结合特异操控神经元活性的光遗传学及化学遗传学技术、病毒示踪技术、离体和在体电生理记录的方法，探讨AD中SUMlPV-dDGPV环路结构和功能的变化与dDG记忆缺失之间的关联、以及光遗传精准靶向SUMlPV-dDGPV环路干预记忆缺失的有效性。这将拓展AD中记忆缺失的神经环路机制，促进精准靶向的脑深部刺激在AD领域应用。

Memory loss is one of the most common clinical symptoms in Alzheimer's disease (AD), which is highly related to hippocampal synaptic degeneration, but the underlying neural circuitries involved are not clear，especially, the relationship between the circuits, which could modulate hippocampal synaptic inputs, and memory loss in AD remain unknown. SUM could modulate the Theta oscillation and enhance synaptic inputs in DG. Our previous work demonstrated that a new circuit in SUM, SUMlPV-dDGPV, which strongly projected to dDG, may be impaired in AD mice models. Based on these work, the proposed study will use a combination of optogenetics and chemogenetics applications, neural tracing technology, and electrophysiological recording methods on AD mice models to study the relationship between the changes in SUMlPV-dDGPV and memory loss in AD, and the effectiveness of intervention in memory loss via an optical treatment that is precisely targeted to SUMlPV-dDGPV. This project will expand the knowledge of neural circuit mechanism of memory loss in AD, and promote the development of deep brain stimulation in AD.