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

 

Abstract

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 ZIcVgluT2 neurons regulated these symptoms. ZIcVgluT2 neuronal activation induced time-locked parkinsonian motor symptoms. In mouse models of PD, the ZIcVgluT2 neurons were hyperactive and inhibition of their activity ameliorated the motor deficits. ZIcVgluT2 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.  

 

Keywords

Parkinson’s disease; Caudal zona incerta;Glutamate; Substantia nigra pars reticulata; Parkinsonian motor symptoms

 

[SpringerLink]