Physiology and Anatomy of the Basal Ganglia

基底神经节的生理学和解剖学

• 批准号: 6824893
• 负责人: Hitoshi Kita
• 金额: $ 22.75万
• 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/6824893
• 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.

我们假设白质外节（the external segment of the pallidum, GPe）位于基底神经节连接的中心，在基底神经节的生理和病理生理中起关键作用。为了理解GPe的神经元活动在生理和病理生理条件下是如何被控制的，必须充分表征GPe神经元的突触输入的性质和突触后膜的性质。解剖学知识和基底神经节运动控制理论预测，大脑皮层的刺激会通过新纹状体（Str）诱导强烈的失突触抑制GPe。然而，在猴单位记录研究和麻醉大鼠的细胞内记录中发现，皮质刺激诱导的GPe抑制很弱，主要是通过丘脑下核（STN）的失突触兴奋。当STN被化学阻断时，皮质刺激诱导长时间的GPe强烈抑制。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。STN阻断也引起GPe神经元缓慢而强烈的振荡。目的2是研究慢振荡的性质。我们在猴子身上的实验也表明，即使在STN阻断后，GPe神经元也能接受强直性兴奋输入。除STN外，GPe可能的兴奋来源还包括中心体-束旁复合体（CM-Pf）和中缝背核。目的3是研究CM-Pf输入GPe的解剖和生理特性。目的4是研究5-羟色胺激动剂对GPe神经元的影响以及对GPe中gaba能突触传递的影响。实验将在大鼠脑切片制备中采用全细胞记录法，在清醒的猴子中采用单元记录法，在大鼠中采用顺行神经示踪法。在提出的项目结束时，我们应该能够为解释突触输入如何控制GPe的神经元活动提供解剖学和生理学基础。