Filion M, Tremblay L, Bédard P J
Centre de Recherche en Neurobiologie, Université Laval et Hôpital de l'Enfant-Jésus, Québec, Canada.
Brain Res. 1988 Mar 15;444(1):165-76. doi: 10.1016/0006-8993(88)90924-9.
Extracellular single unit activity was recorded in the globus pallidus of waking Macaca fascicularis during passive limb movement. The main upper and lower limb joints were investigated bilaterally. The animals were either intact or rendered parkinsonian by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell counts showed that at least 90% of nigral neurons of the compacta-type were degenerated in the parkinsonian animals. In the intact animals, only 17% of the pallidal neurons responded to the natural stimulus. As already reported by others, the responses were typically related to movement about a single contralateral joint and in only one direction. In the parkinsonian animals, however, more neurons responded, often more vigorously, to the same stimulation. In many of these neurons the responses were elicited by movement about more than one joint of both upper and lower limbs or ipsi-and contralateral sides and in more than one direction. The increase in number and magnitude and loss of specificity of responses were much greater in the internal pallidal segment, where the number of responding neurons quadrupled. These results suggest that dopaminergic mechanisms regulate gain and selectivity in the basal ganglia. In animals with decreased dopaminergic functions, the excessive and unselective motor responses may explain all 3 major signs of parkinsonism: rigidity, tremor and akinesia.
在清醒的食蟹猴被动肢体运动期间,记录其苍白球的细胞外单单位活动。双侧研究了主要的上肢和下肢关节。这些动物要么完好无损,要么通过神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导成帕金森病模型。细胞计数显示,在帕金森病模型动物中,至少90%的致密型黑质神经元发生了退化。在完好无损的动物中,只有17%的苍白球神经元对自然刺激有反应。正如其他人已经报道的那样,这些反应通常与对侧单个关节的运动有关,且仅在一个方向上。然而,在帕金森病模型动物中,更多的神经元对相同的刺激有反应,而且反应往往更强烈。在许多这样的神经元中,上肢和下肢或同侧和对侧的多个关节的运动以及多个方向的运动都会引发反应。在内侧苍白球段,反应神经元的数量增加了四倍,反应数量、幅度的增加以及反应特异性的丧失更为明显。这些结果表明,多巴胺能机制调节基底神经节的增益和选择性。在多巴胺能功能降低的动物中,过度且无选择性的运动反应可能解释了帕金森病的所有三大主要症状:僵硬、震颤和运动迟缓。