EXCITATORY SYNAPTIC TRANSMISSION IN NEOSTRIATUM

这项研究项目的目的是为了描述生理学和 兴奋性氨基酸介导突触的药理学研究 在新纹状体中传播。神经化学和电生理学 有证据表明，皮质纹状突触使用谷氨酸或 与它们的神经递质类似的EAA。此外，来自其他地区的传入 大脑区域(例如丘脑底核)也可能兴奋新的纹状体 通过EAA介导的神经元传递。因为皮质传入 构成了新纹状体神经元兴奋性输入的一大来源， 确定这种由EAA介导的传播的特征是 发展对纹状体功能的理解。 众所周知，EAA介导的信息传递可以通过电诱导 大脑皮层或新纹状体本身的刺激。此外， 已证实存在几种类型的EAA受体 新纹状体神经元。然而，还需要进一步的工作来表征 不同受体对突触反应的贡献及其影响 突触激活的不同模式对突触效能的影响 EAA自身受体在调节EAA介导的传递中的作用。因此， 要检验的假设是：1)不同的模式 含EAA的传入神经对纹状体突触的激活 神经元不仅能够产生兴奋性传递，而且 传播中的可塑性变化(例如，依赖于使用的抑郁， 强直后增强)；2)多个EAA受体参与 通过释放内源性神经递质而产生的反应；以及3) 谷氨酸自身受体调节突触释放谷氨酸 纹状体。 有提示证据表明，EAA介导的兴奋性毒性可能 导致涉及纹状体的神经退行性疾病， 尤其是亨廷顿氏症。此外，有可能 作用于EAA受体的药物可以用来调节 患有这种疾病的人的纹状体功能。希望是这样的 EAA介导的生理和药理学的阐明 纹状体中的传播将有助于新的治疗方法 这些障碍。

The aim of the research project is to characterize the physiology and pharmacology of excitatory amino acid (EAA)-mediated synaptic transmission in neostriatum. Neurochemical and electrophysiological evidence indicates that corticostriate synapses use glutamate or a similar EAA as their neurotransmitter. In addition, afferents from other brain regions (e.g. subthalamic nucleus) may also excite neostriatal neurons via EAA-mediated transmission. Since cortical afferents constitute a large source of excitatory input to neostriatal neurons, characterizing this EAA-mediated transmission is a key element in developing an understanding of striatal function. It is known that EAA-mediated transmission can be evoked by electrical stimulation in cortex or within the neostriatum itself. In addition, the presence of several types of EAA receptors has been demonstrated in neostriatal neurons. However, further work is needed to characterize the contribution of different receptors to synaptic responses, the effects of varying patterns of synaptic activation on synaptic efficacy and the role of EAA autoreceptors in modulating EAA-mediated transmission. Thus the hypotheses to be tested are: 1) That different patterns of activation of EAA-containing afferents making synapses onto striatal neurons are capable of producing not only excitatory transmission, but also plastic changes in transmission (e.g. use-dependent depression, posttetanic potentiation); 2) That multiple EAA receptors contribute to responses produced by release of endogenous neurotransmitter; and 3) That glutamate autoreceptors regulate glutamate release from synapses in the striatum. There is suggestive evidence that EAA-mediated excitotoxicity may contribute to neurodegenerative diseases involving the striatum, Huntington's Disease in particular. In addition, it is possible that pharmaceutical agents acting at EAA receptors could be used to modulate striatal function in persons suffering from such disorders. It is hoped that elucidation of the physiology and pharmacology of EAA-mediated transmission in striatum will contribute to new therapeutic approaches to these disorders.