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Functional significance of cortico-subthalamic pathway

皮质底丘脑通路的功能意义

基本信息

批准号：
09680805
负责人：
NAMBU Atsushi
金额：
$ 2.05万
依托单位：
Tokyo Metropolitan Organization for Medical Research (1999)Tokyo Metropolitan Institute for Neuroscience (1997-1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. In the present study, by using awake monkeys, the polysynaptic effects of electrical stimulation in the forelimb regions of the primary motor and primary somatosensory cortices on the activity of globus pallidus (GP) neurons, especially mediated by the subthalamic nucleus (STN), have been characterized. Cortical stimulation induced an early, short-latency excitation followed by an inhibition and a late excitation in neurons of both the external and internal segments of the GP. It also induced an early, short-latency excitation followed by a late excitation and an inhibition in STN neurons. The early excitation in STN neurons preceded that in GP neurons. Blockade of STN neuronal activity by muscimol (GABAィイD2AィエD2 receptor agonist) injection resulted in abolishment of both the early and late excitations evoked in GP neurons by cortical stimulation. At the same time, the spontaneous discharge rate of GP neurons decreased, pauses between the groups of spikes of GP neurons became prominent, and the firing pattern became regular. Injection of CPP (NMDA receptor antagonist), but not NBOX (non-NMDA receptor antagonist), into the STN attenuated the early and late excitations in GP neurons, suggesting that cortico-subthalamic transmission is mediated mainly by NMDA receptors. Interference with the pallido-subthalamic transmission by bicuculline (GABAィイD2AィエD2receptor antagonist) injection into the STN made the inhibition distinct without affecting the early excitation. The present results indicate that the cortico-subthalamo-pallidal pathway conveys powerful excitatory effects from the motor-related cortical areas to the GP with shorter conduction time than the effects conveyed through the striatum.

运动相关皮质区如何调控基底节输出核团的活动，是理解基底节运动控制机制的重要问题。本研究在清醒猴的基础上，研究了电刺激初级运动皮质和初级躯体感觉皮质前肢区域对苍白球(GP)神经元活动的多突触效应，特别是由丘脑底核(STN)介导的效应。大脑皮层刺激在大脑皮层外段和内段的神经元引起早期、短潜伏期的兴奋、随后的抑制和晚期的兴奋。它还在STN神经元中诱导了早期、短潜伏期的兴奋，随后是晚期的兴奋和抑制。STN神经元的早期兴奋先于GP神经元。注射氨基丁酸ィイD2A型ィエD2受体激动剂阻断孤束核神经元的活动，可使皮层刺激引起的早、晚期兴奋消失。同时，GP神经元自发放电率降低，各群峰间歇明显，放电模式变得规则。在STN内注射CPP(NMDA受体拮抗剂)，而不是NBOX(非NMDA受体拮抗剂)，可减弱GP神经元的早期和晚期兴奋，提示皮质-丘脑-下丘脑的传递主要由NMDA受体介导。注射荷包牡丹碱(GABA、ィイ、D2a、ィエ、D2受体拮抗剂)干扰丘脑-苍白球-底核的传递，在不影响早期兴奋的情况下，使抑制作用明显增强。结果表明，皮质-丘脑-下丘脑-苍白球通路从运动相关皮质区向GP传递强大的兴奋效应，其传导时间短于通过纹状体传递的兴奋效应。