Chemogenetic and optogenetic stimulation of zona incerta GABAergic neurons ameliorates motor impairment in Parkinson’s disease

• Published in: iScience 2023-07, Vol.26 (7), p.107149-107149, Article 107149
• Main Authors: Chen, Fenghua, Qian, Junliang, Cao, Zhongkai, Li, Ang, Cui, Juntao, Shi, Limin, Xie, Junxia
• Format: Article
• Language: English
• Subjects: Behavioral neuroscience; Cellular neuroscience; Sensory neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107149

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and leads to progressive motor dysfunction. While studies have focused on the basal ganglia network, recent evidence suggests neuronal systems outside the basal ganglia are also related to PD pathogenesis. The zona incerta (ZI) is a predominantly inhibitory subthalamic region for global behavioral modulation. This study investigates the role of GABAergic neurons in the ZI in a mouse model of 6-hydroxydopamine (6-OHDA)-induced PD. First, we found a decrease in GABA-positive neurons in the ZI, and then the mice used chemogenetic/optogenetic stimulation to activate or inhibit GABAergic neurons. The motor performance of PD mice was significantly improved by chemogenetic/optogenetic activation of GABAergic neurons, and repeated chemogenetic activation of ZI GABAergic neurons increased the dopamine content in the striatum. Our work identifies the role of ZI GABAergic neurons in regulating motor behaviors in 6-OHDA-lesioned PD model mice. [Display omitted] •Zona incerta (ZI) GABAergic neurons impact parkinsonian motor dysfunction•The number of GABA-positive neurons in the ZI was decreased in 6-OHDA-treated mice•Chemogenetic/optogenetic activation of ZI GABAergic neurons improves PD mice locomotion•Chemogenetic repeated activation increases striatal dopamine content Subject areas: Behavioral neuroscience; Cellular neuroscience; Sensory neuroscience.