The Dynamics of Dopamine D_(2) Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats  

作　　者：Kuncheng Liu Miaomiao Song Shasha Gao Lu Yao Li Zhang Jie Feng Ling Wang Rui Gao Yong Wang 

机构地区：[1]Department of Physiology and Pathophysiology and Institute of Neuroscience,School of Basic Medical Sciences,Xi’an Jiao Tong University Health Science Center,Xi’an,710061,China [2]Department of Clinical Medicine,Xi’an Jiao Tong University Health Science Center,Xi’an,710061,China [3]Department of Rehabilitation Medicine,The Second Affiliated Hospital of Xi’an Jiao Tong University,Xi’an,710004,China [4]Department of Medical Imaging and Nuclear Medicine,The First Affiliated Hospital of Xi’an Jiao Tong University,Xi’an,710061,China

出　　处：《Neuroscience Bulletin》2023年第9期1411-1425,共15页神经科学通报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81671109,82071526,and 82071433);the Natural Science Foundation of Shaanxi Province(2021JQ-417).

摘　　要：L-dopa(l-3,4-dihydroxyphenylalanine)-induced dyskinesia(LID)is a debilitating complication of dopamine replacement therapy for Parkinson’s disease.The potential contribution of striatal D_(2) receptor(D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear.In this study,we investigated the role of striatal D_(2)R+neurons and downstream globus pallidus externa(GPe)neurons in a rat model of LID.Intrastriatal administration of raclopride,a D_(2)R antagonist,significantly inhibited dyskinetic behavior,while intrastriatal administration of pramipexole,a D_(2)-like receptor agonist,yielded aggravation of dyskinesia in LID rats.Fiber photometry revealed the overinhibition of striatal D_(2)R+neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats.In contrast,the striatal D2R+neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia.Consistent with the above findings,optogenetic activation of striatal D_(2)R+neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats.Our data demonstrate that the aberrant activity of striatal D_(2)R+neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.

关 键 词：LEVODOPA DYSKINESIA Parkinson's disease D_(2) RECEPTOR Fiber photometry OPTOGENETICS 

分 类 号：R338[医药卫生—人体生理学]