阿尔茨海默病（Alzheimer's disease，AD）是一种非常常见的神经退行性疾病之一，结果会造成认知和记忆功能减退。在AD发病早期就可以出现嗅球缩小及嗅觉功能减退，至今病因未明。GABA是一种抑制性神经递质，在嗅球的颗粒细胞层内存在着大量的GABA能神经元，在对嗅觉信息的调制过程中起着非常重要的作用，但这些GABA能神经元在AD的病理过程中有何改变及扮演什么角色尚不清楚。本项目将利用AD转基因小鼠和GAD67-GFP基因敲入小鼠进行杂交，构建出能特异性表达GAD67-GFP的AD转基因小鼠，研究AD小鼠嗅球颗粒细胞层内GABA能神经元的形态学变化，进一步采用多通道微电极阵列（MEA）结合药理学方法对AD转基因小鼠的嗅球脑片进行实时检测，分析嗅球颗粒细胞层的GABA能神经元的功能改变。研究AD小鼠嗅球内GABA的水平及其调节环路的变化，有助于揭示AD早期出现嗅觉障碍的机制。

Alzheimer's disease (AD) is one of the very common neurodegenerative disease that leads to the loss of cognitive functions and memory impairment.There appears the reduction of volum of olfactory bulb and olfactory dysfunction in early stages of AD, but so far,its etiology is unknown. GABA is an inhibitory transmitter and the granular layer of olfactory bulb is abundant in GABAergic neurons which play an important role in the olfactory processing,however whose role in the pathological mechanism of AD is unclear. In our research we will intercross AD transgenic mouse with laboratory existing GAD67-GFP gene knock-in mouse to construct the special AD transgenic mouses which express GAD67-GFP gene specifically for studying the morphological changes of GABAergic neurons in the granular layer of the AD mouse's olfactory bulb, and for further studying the functional changes of these GABAergic neurons by real-time detection for the AD transgenic mouse's olfactory bulb slices using multi-channel microelectrode array combined with the method of pharmacology. Studying the level of GABA and its regulatory circiuts of AD mouses' olfactory system can be helpful to elucidate the mechanism of olfactory dysfunction in the early stage of AD.