Control of Basal Ganglia Output by Direct and Indirect Pathway Projection Neurons

Control of Basal Ganglia Output by Direct and Indirect Pathway Projection Neurons
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直接和间接通路投影神经元控制基底神经节输出

DOI:
10.1523/jneurosci.1278-13.2013
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发表时间:
2013-11-20
影响因子:
5.3
通讯作者:
Kreitzer, Anatol C.
Kreitzer, Anatol C.
中科院分区:
医学1区
文献类型:
--
作者:
Freeze, Benjamin S.;Kravitz, Alexxai V.;Kreitzer, Anatol C.

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纹状体的直接和间接传出通路最终重新汇聚,影响基底节输出核,进而通过丘脑皮质和脑干运动回路调节行为。然而,这两条传出通路在形成基底节输出中的不同贡献还没有被很好地理解。我们利用对直接和间接通路的选择性光遗传控制,结合在小鼠的基底节输出核黑质网状核(SNR)的单单位记录来研究这些过程。纹状体直接和间接通路投射神经元的光发生激活在SNR神经元中产生不同的细胞反应,刺激每条通路既引起兴奋也引起抑制。尽管反应的异质性,直接通路刺激在产生运动起始方面的有效性选择性地与受抑制的SNR神经元亚群相关。相反,有效的间接通路介导的运动抑制受兴奋的SNR神经元的影响最大。我们的结果支持这样的理论,即关键的基底节输出神经元作为运动输出的抑制门,可以分别通过纹状体直接通路和间接通路来打开或关闭。
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.