EXCITATORY SYNAPTIC TRANSMISSION IN NEOSTRIATUM

该研究项目的目的是描述生理学特征， 兴奋性氨基酸（EAA）介导的突触药理学 在新纹状体的传播。 神经化学和电生理学 有证据表明，皮质纹状体突触使用谷氨酸或 类似于他们的神经递质EAA。 此外，来自其他 大脑区域（例如丘脑底核）也可以激发新纹状体 通过EAA介导的传递。 因为皮层传入神经 构成对新纹状体神经元的兴奋性输入的大来源， 描述EAA介导的传播是一个关键因素， 对纹状体功能的理解 已知EAA介导的传递可以通过电刺激诱发， 刺激皮层或新纹状体本身。 此外该 几种类型的EAA受体的存在已被证明在 新纹状体神经元 然而，还需要进一步的工作来确定 不同受体对突触反应的贡献， 不同的突触激活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， 激活含EAA的传入神经，使突触到达纹状体 神经元不仅能够产生兴奋性传递， 还有传输中的塑性变化（例如依赖于使用的凹陷， 强直后增强）; 2）多种EAA受体有助于 由内源性神经递质释放产生的反应;以及3） 谷氨酸自身受体调节谷氨酸从突触释放， 纹状体 有证据表明EAA介导的兴奋性毒性可能 导致涉及纹状体的神经变性疾病， 尤其是亨廷顿氏病。 此外，有可能， 作用于EAA受体的药剂可用于调节 纹状体的功能。 希望 EAA介导的生理学和药理学的阐明 纹状体中的传递将有助于新的治疗方法 这些疾病。

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.