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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节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。在本研究中，使用清醒的猴子，在前肢区的初级运动和初级躯体感觉皮层的电刺激苍白球（GP）神经元的活动，特别是通过丘脑底核（GNF）介导的多突触效应的特点。皮层刺激诱导的早期，短潜伏期的兴奋，然后抑制和迟兴奋的神经元的外部和内部段的GP。它还诱导了STN神经元的早期、短潜伏期兴奋，随后是晚期兴奋和抑制。海马神经元的早期兴奋早于GP神经元。蝇蕈醇（GABA受体激动剂）注射阻断GP神经元的活动，导致皮层刺激引起的GP神经元的早期和晚期兴奋的取消。与此同时，GP神经元的自发放电频率降低，放电峰群间的停顿变得明显，放电模式变得规则。在中脑腹外侧核内注射NMDA受体拮抗剂CPP（non-NMDA receptor antagonist，NBOX）可减弱GP神经元的早、晚兴奋，提示皮质-底丘脑传递主要由NMDA受体介导。将GABA受体D2 A拮抗剂荷包牡丹碱（bicuculline）注入丘脑底核，干扰苍白球-丘脑底核传递，使抑制作用明显，但不影响早期兴奋。目前的研究结果表明，皮质-丘脑底核-苍白球通路传达强大的兴奋性的影响，从运动相关的皮质区的GP与较短的传导时间比通过纹状体传达的效果。