Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.088351v1?rss=1 Authors: Ducrot, C., Bourque, M.-J., Delmas, C. V. L., Racine, A.-S., Bello, D. G., Delignat-Lavaud, B., Lycas, M. D., Fallon, A., Michaud-Tardif, C., Burke Nanni, S., Herborg, F., Gether, U., Nanci, A., Takahashi, H., Parent, M., Trudeau, L.-E. Abstract: Chemical neurotransmission in the brain typically occurs through synapses, which are structurally and functionally defined as sites of close apposition between an axon terminal and a postsynaptic domain. Ultrastructural examinations of axon terminals established by monoamine neurons in the brain often failed to identify a similar tight pre- and postsynaptic coupling, giving rise to the concept of ''diffuse'' or ''volume'' transmission. Whether this results from intrinsic properties of such modulatory neurons remains undefined. Using an efficient co-culture model, we find that dopaminergic neurons establish an axonal arbor that is distinctive compared to glutamatergic or GABAergic neurons in both size and propensity of terminals to avoid direct contact with target neurons. Furthermore, while most dopaminergic varicosities express key proteins involved in exocytosis such as synaptotagmin 1, only {approx}20% of these are synaptic. The active zone protein bassoon was found to be enriched in a subset of dopaminergic terminals that are in proximity to a target cell. Irrespective of their structure, a majority of dopaminergic terminals were found to be active. Finally, we found that the presynaptic protein Nrxn-1SS4- and the postsynaptic protein NL-1AB, two major components involved in excitatory synapse formation, play a critical role in the formation of synapses by dopamine neurons. Taken together, our findings support the idea that DA neurons in the brain are endowed with a distinctive developmental program that leads them to adopt a fundamentally different mode of connectivity, compared to glutamatergic and GABAergic neurons involved in fast point-to-point signaling. Copy rights belong to original authors. Visit the link for more info