我们上期同名项目取得系列成果：1）生理态分泌调控研究，发现脑片谷氨酸突触上动作电位（AP）调控分泌机制只是AP数目而不是AP时间编码（APTC）；但在体（in-vivo）大脑纹状体的多巴胺分泌却受APTC强烈调控。 2)培养细胞的分泌机制研究，在我室2002发现的电压(而不是钙离子)依赖性分泌CIVDS基础上，新发现静息DRG神经元自发的低频AP（<4Hz）特异触发CIVDS分泌，而疼痛高频刺激主要触发CDS（钙依赖性分泌）；发现同一细胞CIVDS和CDS两种囊泡库相互独立。为扩大我们“生理态单胺分泌”的优势，本申请将集中研究（健康和疾病态）分泌机制：1）在过去12年工作基础上，研究CIVDS分子机制；2）生理（in-vivo和脑片）条件下，研究主要帕金森病动物模型的多巴胺分泌及其相关易感基因致病机理；3) G蛋白受体和钙离子调控量子化分泌的机理。

We have made a series of achievements in previous program with the same name: 1）In the aspect of secretion physiology/translational medicine, we found that the regulation of glutamate secretion in the synapse of calyx mainly depends on the number of action potentials（AP）instead of action potential time coding (APTC) in brain slice. In contrast, dopamine release in striatum of anaesthetic rats in vivo, similar to soma secretion, is strongly regulated by APTC; 2) In the aspect of the mechanism of cell secretion, we made important progresses: In 2002, we found a new and international concerned form of secretion mechanism which is dependent on voltage instead of calcium, and we called it “calcium independent but voltage dependent secretion (CIVDS)”. Spontaneous membrane depolarization with low frequencies (<4Hz) trigger CIVDS, while high frequency stimulations, which can cause pain, trigger CDS (calcium dependent secretion). The two vesicle pools for CIVDS and CDS exist independently in soma of DRG neurons. In order to keep our leading role in the field of “the regulation mechanism of cell secretion (mainly on monoamine neurotransmitters) under physiological condition”, we aim at studying the cellular and molecular regulation mechanisms of cell secretion in more physiological conditions (healthy and sick conditions) in this application: 1) to find out the molecular mechanism of CIVDS and studying its mechanism of function; 2) under physiological conditions (in vivo and brain slice), using major Parkinson’s disease anmal models to real time record APTC induced dopamine release in striatum to study the mechanism of Parkinson’s disease; 3) the regulation mechanism of G protein coupled receptor(GPCR) and calcium on quantal secretion，