Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; Center for Neuroscience, KIST, Seoul 02792, Republic of Korea.
Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea.
Neuron. 2017 Aug 30;95(5):1181-1196.e8. doi: 10.1016/j.neuron.2017.08.028.
Basal ganglia (BG) circuits orchestrate complex motor behaviors predominantly via inhibitory synaptic outputs. Although these inhibitory BG outputs are known to reduce the excitability of postsynaptic target neurons, precisely how this change impairs motor performance remains poorly understood. Here, we show that optogenetic photostimulation of inhibitory BG inputs from the globus pallidus induces a surge of action potentials in the ventrolateral thalamic (VL) neurons and muscle contractions during the post-inhibitory period. Reduction of the neuronal population with this post-inhibitory rebound firing by knockout of T-type Ca channels or photoinhibition abolishes multiple motor responses induced by the inhibitory BG input. In a low dopamine state, the number of VL neurons showing post-inhibitory firing increases, while reducing the number of active VL neurons via photoinhibition of BG input, effectively prevents Parkinson disease (PD)-like motor symptoms. Thus, BG inhibitory input generates excitatory motor signals in the thalamus and, in excess, promotes PD-like motor abnormalities. VIDEO ABSTRACT.
基底神经节 (BG) 回路主要通过抑制性突触输出来协调复杂的运动行为。尽管已知这些抑制性 BG 输出会降低突触后靶神经元的兴奋性,但这种变化如何精确地损害运动性能仍知之甚少。在这里,我们表明,来自苍白球的抑制性 BG 输入的光遗传学光刺激会在抑制后期间诱导腹外侧丘脑 (VL) 神经元中动作电位的激增和肌肉收缩。通过敲除 T 型钙通道或光抑制来减少具有这种抑制后反弹放电的神经元群体,可消除抑制性 BG 输入诱导的多种运动反应。在低多巴胺状态下,表现出抑制后放电的 VL 神经元数量增加,而通过光抑制 BG 输入减少活跃的 VL 神经元的数量,可有效防止帕金森病 (PD) 样运动症状。因此,BG 抑制性输入在丘脑产生兴奋性运动信号,并且过度促进 PD 样运动异常。视频摘要。