Department of Biological Sciences, KAIST, Daejeon 34141, Korea; Center for Neuroscience, KIST, Seoul 02792, Korea.
Department of Biological Sciences, KAIST, Daejeon 34141, Korea.
BMB Rep. 2018 Jan;51(1):3-4. doi: 10.5483/bmbrep.2018.51.1.004.
Parkinson's disease (PD) is a debilitating disorder resulting from loss of dopamine neurons. In dopamine deficient state, the basal ganglia increases inhibitory synaptic outputs to the thalamus. This increased inhibition by the basal ganglia output is known to reduce firing rate of thalamic neurons that relay motor signals to the motor cortex. This 'rate model' suggests that the reduced excitability of thalamic neurons is the key for inducing motor abnormalities in PD patients. We reveal that in response to inhibition, thalamic neurons generate rebound firing at the end of inhibition. This rebound firing increases motor cortical activity and induces muscular responses that triggers Parkinsonian motor dysfunction. Genetic and optogenetic intervention of the rebound firing prevent motor dysfunction in a mouse model of PD. Our results suggest that inhibitory synaptic mechanism mediates motor dysfunction by generating rebound excitability in the thalamocortical pathway. [BMB Reports 2018; 51(1): 3-4].
帕金森病（PD）是一种由多巴胺神经元丧失引起的致残性疾病。在多巴胺缺乏状态下，基底神经节增加了对丘脑的抑制性突触输出。基底神经节输出的这种增加的抑制作用被认为降低了将运动信号中继到运动皮层的丘脑神经元的放电率。这个“速率模型”表明，丘脑神经元兴奋性降低是诱导 PD 患者运动异常的关键。我们揭示，在抑制作用下，丘脑神经元在抑制作用结束时产生反弹放电。这种反弹放电增加了运动皮层的活动，并引起肌肉反应，从而引发帕金森运动功能障碍。对反弹放电的遗传和光遗传学干预可防止 PD 小鼠模型的运动功能障碍。我们的研究结果表明，抑制性突触机制通过在丘脑皮质通路中产生反弹兴奋性来介导运动功能障碍。[BMB 报告 2018；51(1):3-4]。
