老年性痴呆症（AD）是发生在老年期及老年前期的一种神经退行性疾病，早期的主要临床表现为认知功能障碍，尤其是长时记忆形成和维持障碍。随着生活水平的提高和平均寿命的增加，AD越来越成为一个严重的社会问题。然而，迄今还没有一种有效的方法能防治此病，究其主要原因是AD发病的神经机理还远没阐明。通过近四十年的研究，突触可塑性被广泛认为是学习记忆的细胞分子基础，是一个被公认的学习记忆模型。因此，本项目拟从学习记忆的突触可塑性机理方面来探索AD发病的神经机制。我们将在AD转基因小鼠模型上，采用被动逃避行为学方法研究其长时记忆的形成和维持；电生理方法研究海马突触可塑性变化；生化和免疫组化方法分析海马突触小体上及老年斑内PKMζ和AMPA 受体亚单位的表达情况。从而从分子、细胞和整体等不同层面阐述AD发病初期认知功能障碍的突触可塑性机理及其分子机制，为临床防治AD这种神经退行性脑疾病提供新思路和新途径。

Alzheimer's disease (AD), a form of neurodegenerative diseases occurring mostly in senile and presenile, causes cognitive impairment, especially long-term memory formation and maintenance deficit in early-stage patients. With the steady improvement of the standard of living and the simultaneous ageing of the population, AD has become a critical issue for the society. Nevertheless, no cure has been found for AD, mainly because of the lack of understanding of its neuropathological mechanisms. Based on the research of the past 40 years, synaptic plasticity has been widely accepted as the molecular and cellular mechanism underlying learning and memory. This project, therefore, intends to explore the neural mechanisms of AD through the characterization of synaptic plasticity. We will utilize the transgenic mice model of AD to study the formation and maintenance of long-term memory using inhibitory avoidance behavioural tests, to characterize the alteration in hippocampal synaptic plasticity using electrophysiological recordings, and to examine the expression of PKMζ and AMPA subunits in hippocampal synapses as well as senile plaques using biochemical and immunohistological assays. Knowledge gained from this study may thus provide novel approaches to prevent and treat AD in clinical settings by deepening our understanding of the molecular and synaptic mechanisms responsible for the cognitive decline occurring in the early stage of AD at molecular, cellular and whole-organism levels.