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...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.展开更多
基金This work was supported by Key Research and Development Program of Guangdong Province(2019B030335001)the Natural Science Foundation of China(31871070,82090031)+4 种基金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).
文摘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.
