Distinct structural and functional heterogeneity of GABAergic-like dopamine synapses and their alterations in Parkinsonism

Abstract

The dopamine system is essential for governing diverse neural functions, including voluntary movement, reward, motivation, mood, attention, learning, and memory. It is recently known that neurotransmitters such as GABA and glutamate are co-transmitted at dopamine synapses in certain brain regions. Although the roles of neurotransmitter dopamine and dopamine neurons have been intensively studied, the precise molecular structure and physiological function of dopaminergic synapses remain still unclear in various brain regions. Here, we utilized enhanced confocal imaging and electrophysiology combined with optogenetics to dissect structural and functional heterogeneity of dopamine synapses across the brain. We found that dopamine synapses have regional heterogeneity in their distribution and spatial pattern. In addition, these structural features in dopamine synapses correlate with the functional aspects of synaptic transmission in different brain regions. Furthermore, the structure and function of dopamine synapses strongly correlate with GABA co-transmission in health and Parkinsonism. Thus, the differential structure and function of dopamine synapses in distinct brain areas may contribute to the multi-faceted roles of dopamine system in a variety of dopamine-related behaviors.