首页|The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats
The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats
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L-dopa(1-3,4-dihydroxyphenylalanine)-induced dyskinesia(LID)is a debilitating complication of dopa-mine replacement therapy for Parkinson's disease.The potential contribution of striatal D2 receptor(D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear.In this study,we investigated the role of striatal D2R+neurons and downstream globus pal-lidus externa(Gpe)neurons in a rat model of LID.Intras-triatal administration of raclopride,a D2R antagonist,sig-nificantly inhibited dyskinetic behavior,while intrastriatal administration of pramipexole,a D2-like receptor agonist,yielded aggravation of dyskinesia in LID rats.Fiber pho-tometry revealed the overinhibition of striatal D2R+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 D2R+ neurons or their projections in the Gpe was adequate to suppress most of the dyskinetic behaviors of LID rats.Our data demon-strate that the aberrant activity of striatal D2R+ neurons and downstream Gpe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Kuncheng Liu、Miaomiao Song、Shasha Gao、Lu Yao、Li Zhang、Jie Feng、Ling Wang、Rui Gao、Yong Wang
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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
Department of Clinical Medicine,Xi'an Jiao Tong University Health Science Center,Xi'an 710061,China
Department of Rehabilitation Medicine,The Second Affiliated Hospital of Xi'an Jiao Tong University,Xi'an 710004,China
Department of Medical Imaging and Nuclear Medicine,The First Affiliated Hospital of Xi'an Jiao Tong University,Xi'an 710061,China
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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of Shaanxi Province
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