Glutamatergic Neurons in the Caudal Zona Incerta Regulate Parkinsonian Motor Symptoms in Mice  

作　　者：Li-Xuan Li Yu-Lan Li Jin-Tao Wu Ji-Zhou Song Xiao-Ming Li 

机构地区：[1]Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310003,China [2]NHC and CAMS Key Laboratory of Medical Neurobiology,Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration,School of Brain Science and Brain Medicine,Zhejiang University School of Medicine,Hangzhou,310030,China [3]Department of Engineering Mechanics,Soft Matter Research Center,and Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province,Zhejiang University,Hangzhou,310063,China

出　　处：《Neuroscience Bulletin》2022年第1期1-15,共15页神经科学通报（英文版）

基　　金：This work was supported by Key Research and Development Program of Guangdong Province(2019B030335001);the Natural Science Foundation of China(31871070,82090031);Key R&D Program of Zhejiang Province(2020C03009);Science and Technology Program of Guangdong(2018B030334001);Funds for Creative Research Groups of China from the National Natural Science Foundation of China(81521062);Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310023);CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057).

摘　　要：Parkinson’s disease(PD)is the second most common and fastest-growing neurodegenerative disorder.In recent years,it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis.However,little is known about whether and how the caudal zona incerta(ZIc)regulates parkinsonian motor symptoms.Here,we showed that specific glutamatergic but not GABAergic ZIc^(VgluT2) neurons regulated these symptoms.ZIc^(VgluT2) neuronal activation induced time-locked parkinsonian motor symptoms.In mouse models of PD,the ZIc^(VgluT2) neurons were hyperactive and inhibition of their activity ameliorated the motor deficits.ZIc^(VgluT2) neurons monosynaptically projected to the substantia nigra pars reticulata.Incerta-nigral circuit activation induced parkinsonian motor symptoms.Together,our findings provide a direct link between the ZIc,its glutamatergic neurons,and parkinsonian motor symptoms for the first time,help to better understand the mechanisms of PD,and supply a new important potential therapeutic target for PD.

关 键 词：Parkinson's disease Caudal zona incerta GLUTAMATE Substantia nigra pars reticulata Parkinsonian motor symptoms 

分 类 号：R74[医药卫生—神经病学与精神病学]