Two distinct modes of dopaminergic modulation on striatopallidal synaptic transmission

Abstract

Dopamine (DA) and its GPCR receptor control willed movement through D1-direct pathway and D2-indirectpathway within basal ganglia. Although striatopallidal synapses function as a critical gateway of indirect pathway,the physiological functions of dopamine on striatopallidal synapses remain unclear. Here, we seek to understandhow DA through nigropallidal pathway modulates striatopallidal synaptic transmission. We revealed that DA isdirectly released onto the GPe and there is a marked regional heterogeneity of dopaminergic innervation to theGPe. In addition, we found that dopamine D2-like receptors modulate striatopallidal synaptic transmission via twodistinct modes, canonical and non-canonical modes. As potential mechanisms behind distinct modes ofdopaminergic modulation, we further found that D2 and D4 receptors in GPe subregions differentially regulatestriatopallidal synaptic transmission through their differences in subcellular expression and sensitivity. To sum up,these results demonstrate that synaptic information conveyed by indirect pathway can be regulated by DA viatwo distinct modes, which seem to be determined by anatomical locations of striatopallidal synapses in the GPe.Since structural and functional organization of basal ganglia circuits is critical to understanding both DA-relatedbehaviors, our findings will provide new insights into the overlooked role of dopaminergic modulation onstriatopallidal synapses and globus pallidus.