题目：Toward understanding APP function in GABAergic synapse and neuronal circuit
（揭秘淀粉样蛋白前提APP在GABA能突触以及神经环路的功能）
主讲人: 杨莉教授（心理学院教授、博士生导师）
时间：5月29日（周四）下午4点到5点
地点：心理学院大楼301会议室
内容简介：
The neuropathological hallmarks of Alzheimer's disease (AD) are characterized by accumulation of extracellular amyloid plaques along with intraneuronal neurofibrillary tangles, neuronal/ synaptic loss and progressive learning and memory impairment. Beta-amyloid (Aβ) is a cleavage product of amyloid precursor protein (APP). Although much focus has been giving to Aβ in trying to understand the pathogenesis of AD, the function of full-length APP is not fully understood and it is likely that full-length APP performs distinct roles from its cleavage products. Considering the importance of neuronal and synaptic deficits that occurred much earlier than Aβ deposition in the onset and progression of AD, an understanding of how intrinsic-neuronal, synaptic and circultry function is manipulated by APP may reveal how aberrant modulation of APP leads to pathogenesis of AD. We have shown that APP interacts with α1C subunit of L-type voltage-gated calcium channel. APP deficiency results in reduced protein levels of α1C subunit of L-type voltage-gated calcium channel in GABAergic neurons, leading to altered GABAergic short term plasticity. However, the precise role of APP in GABAergic synapse is still unclear. Using electrophysiological, immunohistochemical and molecular biological techaniques, we uncovered important roles of APP in regulating GABAergic synaptic and consequent circuitry activities. APP deficiency results in altered GABAR and KCC2 protein levels, leading to reduced amplitude of GABAAR mediated IPSCs and a positive shift of the GABAAR reversal potential. Furthermore, aberrant cortical network activity observed in mutant was rescued by modulating GABAR activity. In addition to reveal critical role of APP in neuronal function, our findings may have important implications for the understanding of disease mechanisms and therapeutic target in AD.