Chen Hui, Lei Huimeng, Xu Qunyuan
Department of Neurobiology, Beijing Institute of Brain Disorders, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Capital Medical University, Beijing 100069, China.
Behav Brain Res. 2018 Apr 2;341:135-145. doi: 10.1016/j.bbr.2017.12.018. Epub 2017 Dec 29.
Previous studies showed the loss of dopaminergic neurons directly leads to both changes in firing rate and neuronal synchrony in the striatum by pharmacogenetic approach, but physiological observation of striatal neurons in awake animal is rare up to now due to the limitation of recording methods. We use multichannel in vivo recording system, to record the activity pattern of both medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) in awake mouse model of Parkinson's disease (PD), created by injection of 6-hydroxyl-dopamine (6-OHDA) into dorsolateral striatum bilaterally and unilaterally. The abnormal discharge of neurons, including oscillations, burst activity and firing rate were systematically observed, and we used these index together to comprehensively analyse the functional change of striatal neurons in PD mouse model. We found that PD mouse model exhibited elevated synchronized oscillatory activity in β frequency band and decreased firing rate of FSIs during movement. The firing rate and burst activity of MSNs clearly reduced during movement after bilateral dopamine depletion. The present study has novelly shown the firing pattern changes of the MSNs and FSIs in DL striatum in awake PD mouse model, by combination of electrophysiology with molecular biological technology. Our results may help to reveal a new circuitry mechanism of movement disorders in PD.
先前的研究表明，通过药物遗传学方法，多巴胺能神经元的丧失直接导致纹状体放电率和神经元同步性的改变，但由于记录方法的限制，目前在清醒动物中对纹状体神经元的生理学观察很少。我们使用多通道体内记录系统，记录帕金森病（PD）清醒小鼠模型中中型多棘投射神经元（MSNs）和快速放电中间神经元（FSIs）的活动模式，该模型通过双侧和单侧将6-羟基多巴胺（6-OHDA）注射到背外侧纹状体中创建。系统地观察了神经元的异常放电，包括振荡、爆发活动和放电率，并将这些指标结合起来综合分析PD小鼠模型中纹状体神经元的功能变化。我们发现，PD小鼠模型在运动期间β频段同步振荡活动升高，FSIs放电率降低。双侧多巴胺耗竭后，运动期间MSNs的放电率和爆发活动明显降低。本研究通过将电生理学与分子生物技术相结合，首次展示了清醒PD小鼠模型中背外侧纹状体MSNs和FSIs的放电模式变化。我们的结果可能有助于揭示PD运动障碍的新电路机制。
