Striatal Compartmental Control of Movement through Dopamine Inhibition

Authors

• P Li
• SH Pulugulla
• S Das
• J Oh
• R Spolski
• JX Lin
• K Georgopoulos
• WJ Leonard

Abstract

The direct pathway spiny projection neurons (dSPNs), primarily located in the matrix compartment of the dorsal striatum, have been extensively studied for their role in promoting locomotion. However, the contribution of the minority dSPNs in the complementary patch (or striosome) compartment to locomotion remains unclear. In this study, we employed a newly developed knock-in patch mouse strain to investigate the function of patch dSPNs using optogenetic stimulation. Surprisingly, we found that activation of patch dSPNs led to locomotion suppression, in contrast to the effects of matrix dSPNs. Previous research has indicated that patch dSPNs preferentially project to ventral nigral dopaminergic neurons (DANs) and exert robust and prolonged GABAergic inhibition through GABAb receptors. To gain insight into the underlying mechanism of patch-mediated locomotion inhibition, we employed CRISPR/SaCas9-mediated gene targeting to genetically knock down GABAb receptors specifically in DANs. Strikingly, this manipulation completely abolished the locomotion inhibition caused by the activation of patch dSPNs. These intriguing findings unveil a surprising two-level compartmental control mechanism of locomotion. We demonstrate that patch dSPNs exert regulatory control over matrix dSPNs and locomotion by inhibiting the activity of nigral DANs. Our results provide compelling evidence for the intricate interplay between patch and matrix compartments in governing locomotor behavior through the modulation of dopaminergic signaling.

Scientific Focus Area: Neuroscience

This page was last updated on Monday, September 25, 2023