Minister of Education (MOE) Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, Jiangsu Province 210096, China.
School of Information Science and Engineering and Yau Shing-Tung Center, Southeast University, Nanjing 210096, China.
Cell Rep. 2022 Jul 19;40(3):111111. doi: 10.1016/j.celrep.2022.111111.
Enhanced beta oscillations within the cortico-basal ganglia-thalamic (CBT) network are correlated with motor deficits in Parkinson's disease (PD), whose generation has been associated recently with amplified network dynamics in the striatum. However, how distinct striatal cell subtypes interact to orchestrate beta oscillations remains largely unknown. Here, we show that optogenetic suppression of dopaminergic control over the dorsal striatum (DS) elevates the power of local field potentials (LFPs) selectively at beta band (12-25 Hz), accompanied by impairments in locomotion. The amplified beta power originates from a striatal loop driven by somatostatin-expressing (SOM) interneurons and constituted by choline acetyltransferase (ChAT)-expressing interneurons and dopamine D2 receptor (D2R)-expressing medium spiny neurons (iMSNs). Moreover, closed-loop intervention selectively targeting striatal iMSNs or ChATs diminishes beta oscillations and restores motor function. Thus, we reveal a striatal microcircuit motif that underlies beta oscillation generation and accompanied motor deficits upon perturbation of dopaminergic control over the striatum.
增强的皮质基底节丘脑（CBT）网络中的β振荡与帕金森病（PD）的运动缺陷相关，最近的研究表明纹状体中的网络动态放大与运动缺陷相关。然而，不同纹状体细胞亚型如何相互作用以协调β振荡仍然知之甚少。在这里，我们表明光遗传学抑制背侧纹状体（DS）中的多巴胺能控制会选择性地提高局部场电位（LFPs）在β频带（12-25 Hz）的功率，同时运动能力受损。放大的β功率源自由表达生长抑素（SOM）的中间神经元驱动的纹状体环路，由胆碱乙酰转移酶（ChAT）表达的中间神经元和多巴胺 D2 受体（D2R）表达的中间神经元组成。此外，选择性靶向纹状体中间神经元或 ChATs 的闭环干预可减少β振荡并恢复运动功能。因此，我们揭示了一种纹状体微电路模式，该模式是在纹状体多巴胺能控制受到干扰时产生β振荡和伴随的运动缺陷的基础。
