Differential remodeling of subthalamic projections to basal ganglia output nuclei and locomotor deficits in 6-OHDA-induced hemiparkinsonian mice
Ya-Wei Ji,
Xue Zhang,
Jiang-Peng Fan,
Wei-Xin Gu,
Zi-Lin Shen,
Hai-Chuan Wu,
Guiyun Cui,
Chunyi Zhou,
Cheng Xiao
Affiliations
Ya-Wei Ji
School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Xue Zhang
School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221006, China
Jiang-Peng Fan
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory in Brain Diseases, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Wei-Xin Gu
School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Anesthesiology, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, China
Zi-Lin Shen
School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China
Hai-Chuan Wu
School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Anesthesiology, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, China
Guiyun Cui
Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221006, China; Corresponding author
Chunyi Zhou
School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Corresponding author
Cheng Xiao
School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Corresponding author
Summary: The subthalamic nucleus (STN) controls basal ganglia outputs via the substantia nigra pars reticulata (SNr) and the globus pallidus internus (GPi). However, the synaptic properties of these projections and their roles in motor control remain unclear. We show that the STN-SNr and STN-GPi projections differ markedly in magnitude and activity-dependent plasticity despite the existence of collateral STN neurons projecting to both the SNr and GPi. Stimulation of either STN projection reduces locomotion; in contrast, inhibition of either the STN-SNr projection or collateral STN neurons facilitates locomotion. In 6-OHDA-hemiparkinsonian mice, the STN-SNr projection is dramatically attenuated, but the STN-GPi projection is robustly enhanced; apomorphine inhibition of the STN-GPi projection through D2 receptors is significantly augmented and improves locomotion. Optogenetic inhibition of either the STN-SNr or STN-GPi projection improves parkinsonian bradykinesia. These results suggest that the STN-GPi and STN-SNr projections are differentially involved in motor control in physiological and parkinsonian conditions.
