A novel neurotransmitter system involved in the control of motor behavior by the basal ganglia.
A novel neurotransmitter system involved in the control of motor behavior by the basal ganglia.
复制标题
一种新型神经递质系统，参与基底神经节控制运动行为。
DOI：
10.1111/j.1749-6632.1998.tb09081.x
复制
发表时间：
1998
影响因子：
5.2
通讯作者：
Walker,JM
中科院分区：
文献类型：
--
作者：
Sañudo-Peña,MC;Walker,JM
大麻素受体高度集中在基底神经节，1-3一组参与运动控制的脑核团。纹状体和丘脑底核是基底神经节的主要输入，并进而分别构成两个主要输出核，苍白球（GP）和黑质网状（SNr）的主要抑制和兴奋源。[4] GP和SNr中的细胞都具有紧张性活性，它们从丘脑底核接受的兴奋性输入也是如此，[5]分别用于激发或抑制运动的产生。[6]另一方面，纹状体输入主要是沉默的。GP和SNr包含大脑中最高水平的大麻素受体，位于这些结构的输入终端。1-3激活时诱导运动的纹状体或对运动产生相反作用的丘脑底核也富含内源性和可能外源性的大麻素受体。1-4，6下面描述的一组实验旨在将新发现的大麻能神经递质系统纳入基底神经节在运动控制中的作用的现有知识中。为此，进行了两种类型的实验。首先，我们研究了单侧微量注射大麻素到各种基底神经节结构后的转向行为，并研究了大麻素和多巴胺激动剂之间的相互作用。翻转与基底神经节的各种成分的细胞活化或抑制密切相关。一般来说，SNr中的细胞活化导致当活化双侧发生时的运动抑制，或当活化单侧发生时的同侧转向。相反，细胞抑制导致增加的运动或对侧转向时，效果是单向的。第二系列实验检查了（1）大麻素对位于纹状体传出神经末梢到输出核的受体的电生理学作用，以及（2）大麻素受体的作用，大麻素受体被认为位于丘脑底核末梢到输出核，这是前面引用的行为研究提出的一种可能性。鉴于多巴胺损失在帕金森病病因学中的关键作用，8我们采用帕金森病的6-OHDA大鼠模型来确定在这种病理条件下大麻素作用在基底神经节中的运动效应。由于空间的限制，只有一个输出核的数据，SNr，提出。与载体相比，大麻素激动剂CP 55，940的黑质内给药产生对侧旋转（图1A）。在进行这项研究时，9大麻素在黑质中作用的唯一机制是抑制
Cannabinoid receptors are highly concentrated in the basal ganglia, 1–3 a group of brain nuclei involved in the control of movement. The striatum and subthalamic nucleus are major inputs of the basal ganglia, and in turn constitute the major inhibitory and excitatory sources to both major output nuclei, the globus pallidus (GP) and substantia nigra reticulata (SNr), respectively. 4 The cells in both GP and SNr are tonically active, as is the excitatory input they receive from the subthalamic nucleus, 5 and serve to excite or inhibit the production of movement, respectively. 6 On the other hand, the striatal input is mainly silent. 7 The GP and SNr contain among the highest levels of cannabinoid receptors in the brain that are located on input terminals to these structures. 1–3 The striatum, which induces movement when activated, or the subthalamic nucleus, which exerts an opposite effect upon movement, are also rich in cannabinoid receptors of intrinsic as well as possibly extrinsic origin. 1–4, 6 The group of experiments described below aimed to incorporate the newly discovered cannabinergic neurotransmitter system into the current knowledge of the role of the basal ganglia in the control of movement. For this purpose, two types of experiments were performed. First, we examined turning behavior following unilateral microinjections of cannabinoids into various basal ganglia structures, and we examined the interaction between cannabinoids and dopamine agonists. Turning correlates well with the cellular activation or inhibition of various components of the basal ganglia. In general cellular activation in the SNr leads to inhibition of movement when the activation occurs bilaterally, or ipsilateral turning when activation is unilateral. Conversely, cellular inhibition leads to increased movement or contralateral turning when the effect is unilateral. A second series of experiments examined (1) the electrophysiological effects of cannabinoids at receptors located on the terminals of the striatal efferents to the output nuclei, and (2) the actions of cannabinoid receptors thought to be located on the terminals of the subthalamic nucleus to the output nuclei, a possibility suggested from the behavioral studies cited earlier.Finally, in light of the the crucial role of dopamine loss in the etiology of Parkinson’s disease, 8 we employed the 6-OHDA rat model of Parkinson’s disease to determine the motor effects of cannabinoid action in the basal ganglia under this pathological condition. Due to space limitations, only data from one output nuclei, the SNr, are presented. Intranigral administration of the cannabinoid agonist CP55, 940 produced contralateral rotation as compared to vehicle (FIG. 1A). At the time this study was done, 9 the only proposed mechanism of cannabinoid action in the substantia nigra was the inhibition of