"Chemical cocktails: the mechanisms that regulate the release of different chemical signals in the brain"

Matthijs Verhage, Ph.D., Professor of Neuroscience, Center for Neurogenomics and Cognitive Research (CNCR), Vrije Universiteit and VU Medical Center, Amsterdam, The Netherlands The communication between neurons in the brain depends largely on the secretion of a large variety of chemical signals stored in two secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs). The cocktail of chemical signals released from individual neurons is complex and changes drastically with activity (‘chemical frequency coding’). Neuropeptides (incl. neurotrophins like BDNF) are by far the largest group of chemical signals. They are stored in DCVs that travel throughout the neuron and, after being released, influence large groups of receiving neurons. In contrast to our detailed knowledge of synaptic vesicles, very little is known about DCV transport and release mechanisms, their release sites and how the released cocktail of chemical signals changes so drastically with activity. My lab has established new approaches to study intracellular transport and release of these chemical signals in living CNS neurons with single vesicle resolution in vitro and in vivo, and in human, stem cell-derived neurons. In this lecture I will present our most recent findings using these approaches on DCV trafficking and secretion, the molecular factors involved, and the mechanisms underlying chemical frequency coding Persoon, C. M. et al. The RAB3-RIM Pathway Is Essential for the Release of Neuromodulators. Neuron 104, 1065-1080 e1012, doi:10.1016/j.neuron.2019.09.015 (2019). Persoon, C. M. et al. Pool size estimations for dense-core vesicles in mammalian CNS neurons. EMBO J 37, doi:10.15252/embj.201899672 (2018). Emperador-Melero, J. et al. Vti1a/b regulate synaptic vesicle and dense core vesicle secretion via protein sorting at the Golgi. Nat Commun 9, 3421, doi:10.1038/s41467-018-05699-z (2018).