GABAergic-like dopamine synapses in the mouse brain

Abstract

Dopaminergic neurons exist in the midbrain and their axons establish synapses throughout the whole brain. Synaptic transmission at these synapses is crucial for volitional movement and reward-related behaviors, while dysfunction of these synapses causes various psychiatric and neurological disorders. Despite this significance, the brain-wide spatial and functional features of dopamine (DA) synapses remain poorly understood due to difficulties in defining functional DA synapses at the molecular and physiological levels. Here we show that DA synapses are structured and function like GABAergic synapses in the mouse brain. DA transmission is strongly correlated with GABA co-transmission at DA synapses across the brain areas. In addition, functional DA synapses contain GABAergic postsynaptic markers in their postsynaptic membrane and are unevenly distributed throughout the brain with distinct spatial clustering. In the dorsal striatum, GABAergic-like DA synapses are uniquely clustered on the dendrites and GABA transmission at these synapses have disparate physiological properties. Remarkably, the attenuation of GABA co-transmission preceded any deficits in dopaminergic transmission or motor functions of the animal model of Parkinsonism. Our findings show distinct spatial and functional properties of GABAergic-like DA synapses in health and disease. Furthermore, the GABAergic-like features of DA synapses can be utilized to better understand the real complexity of synaptic actions at DA synapses in regulating neural circuits.