Regionally distinct modulation of dopamine on striatopallidal synaptic transmission

Abstract

Basal ganglia are a group of subcortical nuclei, composed of striatum, globus pallidus, subthalamic nucleus, and substantia nigra. The basal ganglia integrate diverse information that is widely distributed over the cortex and filter out the strategy of willed movement. To modulate this system, the neurotransmitter dopamine(DA) from midbrain dopamine neurons is essential. Although the roles of dopamine on the striatum have been intensively studied so far, the physiological functions of dopamine on striatopallidal synapses remain unclear due to relatively sparse dopaminergic innervation on globus pallidus. Here we seek to understand how dopamine through nigropallidal pathway modulates striatopallidal synaptic transmission. Utilizing electrophysiology, optogenetics, enhanced confocal imaging, and synapse analysis, we revealed tat there is a marked regional heterogeneity of dopaminergic innervation on the globus pallidus. In addition, distinct subtypes of dopamine receptors differentially regulated striatopallidal synaptic transmission in a region-specific manner. In a DA-depleted animal model, nigrpallidal dopaminergic fibers innervating each GPe subregion exhibited different susceptibility to 6-OHDA. since structural and functional organization of basal ganglia circuits is critical to understanding both DA-related behaviors and DA-depleted pathological conditions such as Parkinson’s disease, or findings will provide new insights into the overlooked role of dopaminergic modulation on striatopallidal synapses and globus pallidus.