Dissection of Striatal Dopamine Hub Synapses in Physiology and Models of Addiction. – DopamineHub

The neuromodulator dopamine controls reward, motivation, attention, and motor skills and is implicated in addiction. Dopamine neurons extend their axons in very large areas of the brain, especially in the striatum. However, the molecular and functional properties of dopaminergic terminals have remained elusive due to a lack of good purification of this rare population of synapses and the lack of a good in vitro model. To circumvent this we purified dopaminergic synaptosomes using fluorescence activated synaptosome sorting. Our ex-vivo model revealed an overview of the molecular connectome of dopamine varicosities and unraveled the existence of associations between dopamine and excitatory (glutamatergic) or inhibitory (GABAergic) synapses. We called these structures “hub synapses”. We also identified a synaptic adhesion protein highly enriched at dopaminergic synaptosomes. DopamineHub will dissect the proteomics, cellular and functional features of dopaminergic synapse hubs in purified synaptosomes and intact tissue at basal state, under depletion of the newly identified synaptic adhesion protein and following exposure to cocaine as a model of plasticity. DopamineHub will unravel the first cellular and molecular map of the dopaminergic synapse hubs in physiology and pathology.