Gladstone Institute of Neurological Disease, San Francisco, California 94158, Biomedical Sciences Program and Medical Scientist Training Program, University of California, San Francisco, California 94117-1049, Department of Psychology, and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109-1340, and Departments of Physiology and Neurology, University of California, San Francisco, California 94117-1049.
J Neurosci. 2013 Nov 20;33(47):18531-9. doi: 10.1523/JNEUROSCI.1278-13.2013.
The direct and indirect efferent pathways from striatum ultimately reconverge to influence basal ganglia output nuclei, which in turn regulate behavior via thalamocortical and brainstem motor circuits. However, the distinct contributions of these two efferent pathways in shaping basal ganglia output are not well understood. We investigated these processes using selective optogenetic control of the direct and indirect pathways, in combination with single-unit recording in the basal ganglia output nucleus substantia nigra pars reticulata (SNr) in mice. Optogenetic activation of striatal direct and indirect pathway projection neurons produced diverse cellular responses in SNr neurons, with stimulation of each pathway eliciting both excitations and inhibitions. Despite this response heterogeneity, the effectiveness of direct pathway stimulation in producing movement initiation correlated selectively with the subpopulation of inhibited SNr neurons. In contrast, effective indirect pathway-mediated motor suppression was most strongly influenced by excited SNr neurons. Our results support the theory that key basal ganglia output neurons serve as an inhibitory gate over motor output that can be opened or closed by striatal direct and indirect pathways, respectively.
纹状体的直接和间接传出通路最终重新汇聚,以影响基底神经节输出核,进而通过丘脑皮质和脑干运动回路调节行为。然而,这两种传出通路在塑造基底神经节输出方面的独特贡献尚不清楚。我们使用对直接和间接通路的选择性光遗传学控制,结合在小鼠基底神经节输出核(黑质网状部)中的单细胞记录,研究了这些过程。光遗传学激活纹状体的直接和间接通路投射神经元,在 SNr 神经元中产生了不同的细胞反应,刺激每条通路都会引起兴奋和抑制。尽管存在这种反应异质性,但直接通路刺激在产生运动起始方面的有效性与被抑制的 SNr 神经元亚群选择性相关。相比之下,间接通路介导的有效运动抑制受兴奋的 SNr 神经元的影响最大。我们的结果支持这样一种理论,即关键的基底神经节输出神经元作为对运动输出的抑制性门控,分别由纹状体的直接和间接通路打开或关闭。