ROLE OF ATP IN NEUROTRANSMISSION

这项工作的目标是确定ATP在突触中的作用 中枢神经系统的神经传递和突触效率。这些研究将 在海马区和纹状体脑片上进行。我们最近发现了一个 突触前终末钙依赖的ATP释放 强烈刺激Schaffer侧支(Sch.coll.)在试管中。高 同时诱发ATP释放的频率刺激 永久性的变化 在突触效率上。这种现象被称为长期 增强(LTP)，被普遍认为是测试 内存的属性。外源性三磷酸腺苷作用于大鼠海马脑片 释放实验中观察到的浓度(NM范围) 永久性地提高了突触效率。我的假设是，ATP 强烈刺激时的释放触发LTP和LTP的变化 可能与记忆的形成有关。本研究将集中于 两个问题：A/ATP释放机制的进一步表征，以及B/ 这种机制，通过它，三磷酸腺苷可以加强突触反应。这就做 确定使用不同传输器的突触 显示LTP(纹状体神经元与海马区)的能力不同 神经元)，以类似的方式释放三磷酸腺苷。为了更好地刻画 释放三磷酸腺苷、抑制剂和抗体对胞外钙离子的代谢 ATPase(导致细胞内ATP分解的主要酶) 细胞外空间)将被使用。此外，生化研究将 以确定观察到的生化事件是否 电诱发LTP诱发的增强效应。这些研究将是 与电生理记录相关。钙 将评估内源性谷氨酸的积累、释放和吸收 在不同浓度的ATP孵育的切片中。激酶C 所调节的磷酸肌醇水解物是根据 目前的概念，LTP中的一个关键酶。一项发布的建议 三磷酸腺苷可以通过修饰激酶C来诱导LTP，活性将被检测。这个 三磷酸腺苷对突触电位的影响将有助于发现三磷酸腺苷在脑内的作用。 突触可塑性和记忆的分子机制。

The objectives of the work are to establish the role of ATP in synaptic neurotransmission and synaptic efficiency in the CNS. These studies will be conducted on hippocampal and striatal slices. We recently found a calcium-dependent release of ATP from presynaptic terminals following intense stimulation of Schaffer collaterals (Sch.coll.) in vitro. High frequency stimulation which evokes ATP release simultaneously induced permanent changes in the synaptic efficiency. This phenomenon, called long-term potentiation (LTP), is generally accepted as a good model for testing the properties of memory. Exogenous ATP applied to the hippocampal slices at the concentration observed in the release experiments(nM range) permanently enhanced synaptic efficiency. My hypothesis is that ATP release during intense stimulation triggers changes involved in LTP and may be related to memory formation. The present study will concentrate on two problems : A/further characterization of ATP release mechanism, and B/ the mechanism, through which ATP can potentiate synaptic response. I will determine if the synapses which use different transmitters and have different ability to show LTP (striatal neurons versus hippocampal neurons), release ATP in a similar way. In order to better characterize the metabolism of release ATP, inhibitors and antibody towards ecto-Ca2+- ATPase (the main enzyme responsible for the ATP breakdown in the extracellular space) will be used. In addition, biochemical studies will be conducted to determine if biochemical events observed after electrically evoked LTP evoked potentiation. These studies will be correlated with electrophysiological recordings. The calcium accumulation, release and uptake of endogenous glutamate will be evaluated in the slices incubated with different ATP concentrations. Kinase C regulated by products of phosphoinositol hydrolysis is according to current concepts, a key enzyme engaged in LTP. A suggestion that released ATP can induce LTP by modifying the kinase C activity will be tested. The effect of ATP on synaptic potentials will help find the role of ATP in molecular mechanism of synaptic plasticity and memory.