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.

我们假设颗粒的外部段（GPE）位于基底神经节连接的中心，在基底神经节的生理学和病理生理学中起关键作用。 为了了解如何在生理和病理生理条件下控制GPE的神经元活性，应充分表征GPE神经元突触输入的性质和突触后膜的特性。 解剖学知识以及基础神经节运动控制的理论预测，大脑皮层的刺激将通过Neostriatdum（STR）诱导强大的脱节，在GPE中抑制。 然而，在猴子单位记录研究中获得的引人注目的观察以及麻醉大鼠的细胞内记录是，皮质刺激诱导的GPE抑制作用较弱，并且通过丘脑下核（STN）的双突触激发主导。当STN化学封闭时，皮质刺激在GPE中诱导了长时间的强大抑制作用。 因此，目标1是测试谷氨酸能输入抑制GPE中GABA能抑制的可能性。 STN封锁还引起了GPE神经元的缓慢且强烈的振荡。 目标2是研究缓慢振荡的性质。 我们在猴子中的实验还表明，即使在STN封锁之后，GPE神经元也接受了补品兴奋性输入。 除STN以外，GPE的可能的兴奋能源包括Centromedian-Parafascicular络合物（CM-PF）和背侧Raphe核。 目的3是研究GPE的CM-PF输入的解剖学和生理特性。 目标4是研究5-HT激动剂对GPE神经元以及GPE中GABA能突触传播的影响。实验将在大鼠脑切片制剂中使用全细胞记录方法，清醒猴子中的单位记录方法以及大鼠中的顺行神经激素方法。 在拟议项目的结尾，我们应该能够提供解剖学和生理基础，以解释突触输入如何控制GPE的神经元活动。