Regionally distinct modulation of dopamine on striatopallidal synaptic transmission

Dopamine (DA) neurons exist in a small number primarily in the midbrain areas, substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Despite the small cell number, DA neurons project their axons to diverse target areas through huge axonal arborization, establishing many DA synapses across the brain. Nigrostriatal and mesocorticolimbic pathways are two major DA projections targeting striatum, cortex, and limbic areas. Although the roles of DA pathways, especially nigrostriatal and mesocorticolimbic pathways, have been intensively studied mostly in the striatum, DA neurons are also known to project directly to extrastriatal basal ganglia nuclei such as globus pallidus (GP) via nigropallidal pathway. However, compared with other DA pathways, the physiological role of DA projection on the regulation of GP neural circuits remains poorly understood. Here we seek to understand how DA through nigropallidal pathway modulates striatopallidal synaptic transmission. Utilizing electrophysiology, optogenetics, enhanced confocal imaging, and synapse analysis, we revealed that there is a marked regional heterogeneity of dopaminergic innervation to globus pallidus. In addition, distinct subtypes of dopamine receptors differentially regulated striatopallidal synaptic transmission in a region-specific manner. Since striatopallidal synapses function as a critical gateway of indirect pathway in the basal ganglia circuitry, our findings will provide new insights into the overlooked role of dopaminergic modulation on striatopallidal synapses and globus pallidus