A striatal SOM-driven ChAT-iMSN loop generates beta oscillations and produces motor deficits

Dandan Qian; Wei Li; Jinwen Xue; Yi Wu; Ziling Wang; Tao Shi; Songting Li; Jingxuan Yang; Shi Qiu; Shaoli Wang; Yousheng Shu; Liang Chen; Qiao Wang; Ti-Fei Yuan; Douglas Zhou; Wei Lu

doi:10.1016/j.celrep.2022.111111

A striatal SOM-driven ChAT-iMSN loop generates beta oscillations and produces motor deficits

Cell Rep. 2022 Jul 19;40(3):111111. doi: 10.1016/j.celrep.2022.111111.

Authors

Dandan Qian¹, Wei Li¹, Jinwen Xue¹, Yi Wu², Ziling Wang³, Tao Shi³, Songting Li³, Jingxuan Yang¹, Shi Qiu¹, Shaoli Wang⁴, Yousheng Shu⁵, Liang Chen⁵, Qiao Wang², Ti-Fei Yuan⁶, Douglas Zhou⁷, Wei Lu⁸

Affiliations

¹ 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.
² School of Information Science and Engineering and Yau Shing-Tung Center, Southeast University, Nanjing 210096, China.
³ School of Mathematical Sciences, Ministry of Education-Key Laboratory of Scientific and Engineering Computing and Shanghai Frontier Science Center of Modern Analysis, Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
⁴ 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; Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
⁵ Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
⁶ Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
⁷ School of Mathematical Sciences, Ministry of Education-Key Laboratory of Scientific and Engineering Computing and Shanghai Frontier Science Center of Modern Analysis, Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: [email protected].
⁸ 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; Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China. Electronic address: [email protected].

PMID: 35858550
DOI: 10.1016/j.celrep.2022.111111

Abstract

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.

Keywords: CP: Neuroscience; ChAT cells; SNc; SOM cells; beta oscillations; striatum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basal Ganglia
Choline O-Acetyltransferase*
Corpus Striatum*
Dopamine
Interneurons / physiology

Substances

Choline O-Acetyltransferase
Dopamine