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.

运动相关皮层区域如何调节基底神经节核输出的活动是理解基底神经节运动控制机制的一个重要问题。在本研究中，通过使用清醒的猴子，研究电刺激的多突触效应。初级运动皮质和初级躯体感觉皮质的前肢区域中苍白球（GP）神经元的活动，尤其是由丘脑底核（STN）介导的皮质，已经得到了表征。刺激诱导了 GP 外部和内部节段神经元的早期、短潜伏期兴奋，随后是抑制和晚期兴奋。它还诱导了 STN 中的早期、短潜伏期兴奋，随后是晚期兴奋和抑制。 STN 神经元的早期兴奋先于 GP 神经元，通过注射蝇蕈醇（GABA-D2A-D2 受体激动剂）阻断 STN 神经元活动，导致早期和晚期兴奋消失。同时，GP神经元的自发放电率降低，GP神经元尖峰组之间的停顿变得明显，并且注射CPP（NMDA受体拮抗剂）的放电模式变得规则。但 NBOX（非 NMDA 受体拮抗剂）进入 STN 会减弱 GP 神经元的早期和晚期兴奋，这表明皮质-底丘脑传递主要是由 NMDA 受体的干扰介导的。通过将荷包牡丹碱（GABA-D2A-D2 受体拮抗剂）注射到 STN 中，苍白球-底丘脑传递产生明显的抑制作用，而不影响早期兴奋。目前的结果表明，皮质-底丘脑-苍白球通路传递来自运动相关的强大兴奋作用。皮质区域到 GP 的传导时间比通过纹状体传达的效果要短。