Neurosecretion: from memory to mood disosders
Nerve cells in our brain send out a large variety of chemical signals: classical neurotransmitters for the ultrafast one-on-one signaling between neurons in synapses, but also many neuropeptides, which can act over large distances, activating many different target cells inside and outside our brain. Neuropeptides exert a strong influence on our behavior and our feelings, such as hunger or satiety, arousal, euphoria or pain, but also on brain plasticity, on cognition and regeneration after injury. Defects in neuropeptide release are considered to be central in many diseases, from diabetes and obesity to memory- and mood disorders.
Neuropeptides are stored inside nerve cells in specialized ‘dense core vesicles’ (DCVs). How, where and when these vesicles release their content is the main topic of a project financed with an ERC Advanced Grant. It is already clear that the molecular mechanisms of DCV release differ considerably from those of classical neurotransmitters, but furthermore not a lot is known. In addition to neuropeptides, many other cellular components appear to be released by DCVs, such as enzymes involved in brain plasticity or protein-machines that may generate new synaptic release sites.
The project will exploit living neurons in culture, also human neurons from patients, by reprogramming human fibroblasts, and new photonic approaches to monitor DCVs trafficking and release inside living neurons with single vesicle resolution. The overall aim of this project is to characterize DCV trafficking and release, the genes/proteins involved and how these processes can be engineered to assist regeneration after injury or disease.