轻度认知障碍（MCI）是一种介于正常老化和痴呆之间的临床状态，被认为是阿尔茨海默病（AD）的前驱性阶段。临床研究表明伴发抑郁是促进MCI向AD转化的一个关键病理因素，但MCI介导抑郁行为变化的关键脑区及作用机制尚不清楚。在前期工作中我们应用了低月龄的APP/PS1小鼠作为AD早期MCI阶段的模型，发现2-3月龄APP/PS1小鼠具有抑郁样表型；小鼠的前额叶皮层（PFC）有少量Aβ沉积，脑区的兴奋性增强，提示该脑区在MCI伴发抑郁中具有关键作用；PFC脑区的GABA递质传递受损，可能是MCI导致抑郁行为的病理生理机制。本研究拟采用2-3月龄的APP/PS1小鼠，通过运用行为学、全细胞膜片钳、光遗传学以及分子生物学等技术手段，探讨前额叶皮层GABA递质传递受损在MCI伴发抑郁中的病理作用以及可能的分子机制，为MCI伴发抑郁的干预提供新的理论依据和策略。

Mild cognitive impairment (MCI) is a clinical condition between normal aging and dementia, which is considered to be a progenitor stage of Alzheimer's disease (AD). Clinical studies showed that depression is a key pathological factor in promoting the progression of MCI to AD, but the key brain regions and mechanisms of MCI with depression are still unclear. In the previous work, we applied young APP/PS1 mice as a model of MCI, and found that 2-3 months old APP/PS1 mice have depression-like behavior, a small amount of Aβ deposition, impaired synaptic inhibitory transmission and increased excitability of pyramidal neurons were detected in the prefrontal cortex (PFC) of these mice, suggesting that PFC plays an important role in MCI with depression. Impaired GABA transmission in PFC may be the pathophysiological mechanism of MCI leading to depression-like behavior. In this study, we aim to use 2-3 months old APP/PS1 mice as MCI with depression model, and preliminarily clarify prefrontal cortical inhibitory dysfunction by using behavioral test, whole cell patch-clamp, optogenetics and molecular biology. The role of impaired function in MCI with depression and its mechanisms would provide new ideas and strategies for MCI with depression treatment.