The molecular mechanisms of aminergic release at “en-passent” type II synaptic terminals of the fruit fly (Drosophila melanogaster).

点击翻译按钮获取中文摘要

The proposal will yield insights into the structural and functional plasticity driving the interplay between type I and aminergic type II synaptic terminals. We particularly seek to understand how neuromodulation emanating from type II terminals impacts on the fast synaptic vesicle release of type I terminals also known as neuromuscular junctions (NMJ).Due to their peripheral location, these synapses are easily accessible and, thus, serve as an ideal example for similar interactions in the less accessible brain where modulation of synapses is a major means for learning processes. Synapses of the neuromodulatory neurons themselves, in Drosophila larvae known as type II synaptic terminals are much less studied compared to synapses of motor neurons called type I terminals (or NMJ, neuromuscular junction). In particular, the mechanism of exocytosis of the type II synaptic terminals formed by the axons of tyraminergic/octopaminergic unpaired median neurons are in the focus of our experiments. These type II terminals form synapses of the “en-passent”-type, contain dense core vesicles and modulate the efficacy of transmission by NMJs. Whether these type II-terminals use scaffold-proteins to form active zone-type cytomatrices remains unknown, however. This question will be rigorously explored by a combination of immunocytochemistry, ultrastructural analysis including immunogold labeling and, importantly, super resolution light microscopy, following protocols well established in the Sigrist lab. As an essential aspect for deeper understanding, will seek to study the developmental interplay between of type I and II terminals, particularly during metamorphosis, so far a terra incognita. Particularly, whether interactions between motor and neuromodulatory neurons and their terminals during metamorphosis are necessary in order to establish fully functional “proper” NMJs and “en-passant”-synapses (type II terminals) in the adult muscle is in the focus here. Throughout, we shall use a behavioral read out for functional importance: (i) larval crawling and (ii) adult stationary flight.