Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
J Neurosci. 2011 Jul 13;31(28):10311-22. doi: 10.1523/JNEUROSCI.0915-11.2011.
The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.
大脑运动皮层（MC）向基底节（BG）发送大量投射。帕金森病（PD）患者和动物模型的运动障碍可能是由于多巴胺（DA）耗竭的基底节异常处理来自 MC 的信息所致。为了研究 DA 耗竭如何改变基底节中的信号传递，我们在异氟烷麻醉的对照和 6-羟多巴胺处理的半帕金森大鼠的基底节中记录了 MC 刺激诱导的（MC 诱导的）单位反应。本报告描述了关于 DA 耗竭如何改变 MC 诱导反应的新发现。MC 刺激在正常静止的纹状体（Str）神经元中引发兴奋，这些神经元投射到苍白球外部段（GPe）。DA 耗竭后，Str-GPe 神经元的自发放电增加，MC 刺激引发潜伏期较短的兴奋，随后是长时间的抑制，在正常情况下这种抑制是不可见的。增加的放电活动和新暴露的长抑制在 GPe 中产生紧张抑制和去易化。GPe 中的去易化然后在基底节回路中被放大，并在基底节输出核，即苍白球内部段中产生强大的长抑制。在 Str 内注射行为有效剂量的 DA 前体 l-3,4-二羟基苯丙氨酸可有效逆转这些变化。这些新观察到的机制也支持了帕金森病患者基底节中常见的停顿和爆发活动的产生。这些结果表明，基底节中异常反应序列的产生导致 PD 中运动障碍的发展，而 Str 内的 DA 补充有效地抑制了异常信号传递。
