THALAMOSTRIATAL SYSTEM IN PARKINSONISM

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这些研究考察了正常和帕金森病猴丘脑板内核(即中央正中核和束旁核(CM/PF))与纹状体之间的功能相互作用和联系的解剖。从CM到壳核的投射优先终止于胆碱能纹状体间神经元，然后在正常和病理条件下形成纹状体输出。我们已经发现，在短刺激序列的刺激下，CM电刺激在纹状体细胞中导致复杂的激活和抑制序列，最可能的是通过局部抑制性轴突侧支和胆碱能中间神经元在纹状体内传播活动和加工。 由于抑制性刺激反应可能是由GABA能固有纹状体神经元介导的，我们正在研究GABA能神经元的轴突侧支与胆碱能神经元的终末模式。我们发现，这些轴突侧支的很大一部分确实终止于胆碱能中间神经元。我们还继续研究了两种动物的纹状体神经元对CM刺激的电生理反应。在我们的实验中，至少有一部分这样的反应可以被谷氨酸或GABA能药物阻断，但不能被乙酰胆碱受体阻滞剂阻断。最后，我们已经开始研究帕金森病(MPTP治疗)猴子板层内核团神经元数量的变化。这些研究(到目前为止，在1只对照组和4只接受MPTP治疗的猴子中)表明，MPTP治疗导致椎板内核神经元减少55%-60%。这种神经元的缺失可能会对帕金森症患者的纹状体功能产生重大影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. These studies examine the functional interactions and the anatomy of the connections between the intralaminar nuclei of the thalamus (i.e., the centromedian and parafascicular nuclei (CM/PF)) and the striatum in normal and parkinsonian monkeys. Projections from the CM to the putamen terminate preferentially on cholinergic striatal interneurons which may then shape striatal output under normal and pathologic conditions. We have found that electrical CM stimulation with short trains of stimuli results in complex sequences of activation and inhibition in striatal cells, most likely through intrastriatal spread of activity and processing through local inhibitory axon collaterals and cholinergic interneurons. As the inhibitory stimulation responses may be mediated by GABAergic intrinsic striatal neurons, we are examining the termination patterns of axon collaterals of such GABAergic neurons onto cholinergic neurons. We found that a large proportion of these axon collaterals indeed terminates on the cholinergic interneurons. We also continued with our studies of the electrophysiologic responses of striatal neurons to CM stimulation in two animals. At least a subset of such responses can be blocked in our experiments by glutamatergic or GABAergic drugs, but not by acetylcholine receptor blockers. Finally, we have begun to study changes in the number of neurons in the intralaminar nuclei in parkinsonian (MPTP-treated) monkeys. These studies (thus far in 1 control, and 4 MPTP-treated monkeys) show that MPTP-treatment leads to a 55-60% reduction of neurons in the intralaminar nuclei. Loss of such neurons may have a major impact on striatal functioning in parkinsonism.