Two distinct modes of dopaminergic modulation on striatopallidal synaptic transmission in health and diseases

Abstract

Dopamine (DA) and its G-protein-coupled receptors (GPCRs) control willed movement through the D1-direct pathway and D2-indirect pathway within the basal ganglia. In a classical model, excessive activity in the indirect pathway is one of the circuit mechanisms underlying parkinsonism. Although striatopallidal synapses serve as a critical gateway of the indirect pathway, the physiological functions of dopamine on striatopallidal transmission remain poorly understood. Here, we sought to understand how DA through the nigropallidal pathway modulates striatopallidal transmission. We found that striatopallidal synapses region-specifically modulate indirect pathway via directly released dopamine on the GPe. Notably, 6-OHDA-induced DA depletion particularly promotes D2R-mediated presynaptic inhibition in ventrolateral and dorsomedial subregions of the GPe. To sum up, these results demonstrate that synaptic information conveyed by the indirect pathway can be differentially regulated by DA via distinct modes of action in the GPe subregions, which can be determined by anatomical locations of striatopallidal synapses.