Physiology and Anatomy of the Basal Ganglia

基底神经节的生理学和解剖学

• 批准号: 6421775
• 负责人: Hitoshi Kita
• 金额: $ 22.67万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-15 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6421775
• 关键词: AMPA receptors; Macaca; NMDA receptors; basal ganglia; brain electrical activity; brain mapping; central neural pathway /tract; dorsal raphe nucleus; excitatory aminoacid; glutamates; histology; laboratory rat; lenticular nucleus; neural information processing; neurophysiology; putamen; serotonin; thalamus

We have hypothesized that the external segment of the pallidum (GPe) is located at the center of the basal ganglia connections and plays a key role in the physiology and pathophysiology of the basal ganglia. To understand how the neuronal activity of the GPe is controlled under physiological and pathophysiological conditions, the nature of both the synaptic inputs to the GPe neurons and the properties of the postsynaptic membrane should be fully characterized. Anatomical knowledge as well as theories on the basal ganglia motor control predict that the stimulation of the cerebral cortex would induce powerful disynaptic, through the neostriatdum (Str), inhibition in the GPe. However, a striking observation obtained in monkey unit recording study as well as intracellular recording in anesthetized rats was that the cortical stimulation-induced inhibition in the GPe was weak and was dominated by the disynaptic excitation through the subthalamic nucleus (STN). When the STN was chemically blocked, cortical stimulation induced a long duration powerful inhibition in the GPe. Thus, aim 1 is to test a possibility that glutamatergic inputs suppress GABAergic inhibition in the GPe. The STN blockade also caused slow and strong oscillation of GPe neurons. Aim 2 is to investigate the nature of the slow oscillation. Our experiments in the monkey also suggest that GPe neurons receive tonic excitatory input even after the STN blockade. The possible excitatory sources to the GPe, other than the STN, include the centromedian-parafascicular complex (CM-Pf) and the dorsal raphe nucleus. Aim 3 is to study the anatomical and physiological properties of the CM-Pf inputs to the GPe. Aim 4 is to investigate the effects of 5-HT agonists on the GPe neurons and also on the GABAergic synaptic transmissions in the GPe. Experiments will use whole cell recording method in rat brain slice preparations, unit recording method in awake monkeys and an anterograde neurotracing method in the rat. At the end of the proposed projects, we should be able to offer an anatomical and physiological basis for explaining how the synaptic inputs might control the neuronal activity of the GPe.

我们假设苍白球外段（GPe）位于基底节连接的中心，在基底节的生理和病理生理中起着关键作用。 为了了解GPe的神经元活动是如何在生理和病理生理条件下控制的，GPe神经元的突触输入的性质和突触后膜的性质应充分表征。 解剖学知识以及关于基底神经节运动控制的理论预测，大脑皮层的刺激将通过新纹状体（Str）在GPe中诱导强大的双突触抑制。 然而，在猴单位记录研究以及麻醉大鼠细胞内记录中获得的一个引人注目的观察结果是，在GPe中皮层刺激诱导的抑制是弱的，并且由通过丘脑底核（subthalamic nucleus，简称TH）的双突触兴奋所支配。化学阻断GPe后，刺激皮层可引起GPe长时间的强抑制。 因此，目的1是测试谷氨酸能输入抑制GPe中GABA能抑制的可能性。 阻断GPe还可引起GPe神经元缓慢而强烈的振荡。 目的二是研究慢振荡的性质。 我们在猴子身上的实验还表明，GPe神经元即使在阻断多巴胺后也能接受紧张性兴奋性输入。 GPe可能的兴奋源除延髓外，还包括中央-束旁复合体（CM-Pf）和中缝背核。 目的3研究CM-Pf传入GPe的解剖学和生理学特性。 目的4研究5-HT激动剂对GPe神经元及GABA能突触传递的影响。实验将在大鼠脑片制备中使用全细胞记录法，在清醒的猴子中使用单位记录法，在大鼠中使用顺行神经示踪法。 在建议的项目结束时，我们应该能够提供一个解剖学和生理学基础，解释突触输入如何控制GPe的神经元活动。