GABAergic-like dopamine synapses in health and Parkinsonism

Abstract

Dopamine synapses play a crucial role for volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, true biological nature of dopamine synapses remains poorly understood in the brain. Here we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses are structured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are uniquely clustered on the dendrites and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in an animal model of Parkinsonism. Our findings reveal unknown spatial and functional nature of GABAergic-like dopamine synapses in health and disease.