Synaptic and supra-synaptic organisation of the dopaminergic projection to the striatum.

Dopamine transmission is a monoaminergic system involved in reward processing and motor control. Volume transmission is thought to be the main mechanism by which monoamines modulate effector transmission though synaptic structures are scarcely described. Here, we applied a fluorescence activated synaptosome sorting workflow to dopaminergic projections to the striatum and explored cellular and molecular features of the dopaminergic synaptome. This demonstrated that dopaminergic varicosities adhere to post-synaptic membrane baring cognate receptors. We further identified a specific bond of varicosities to glutamatergic or GABAergic synapses in structures we named dopaminergic hub synapses. Finally, we showed that the synaptic adhesion protein SynCAM 2 is strongly expressed at dopaminergic hub synapses. Our data strongly suggest that neuromodulation frequently operates from hub-synapses on local receptors, presumably in conjunction with extra-synaptic volume transmission. We provide a new framework for the molecular exploration of dopaminergic synapses and more generally on discrete synapse populations ex-vivo.