Novel in vitro platform to study molecular mechanisms of neurotransmitter release and synaptic plasticity

Why did we fund this project?

This award aims to replace some experiments in neurons prepared from brain tissue by developing an in vitro platform to study neurotransmitter release.

Neurons communicate with each other at synapses by releasing neurotransmitters stored in synaptic vesicles. This process is controlled by neuronal electrical activity and changes in calcium concentration, and is disrupted in many neurological disorders. The mechanisms of neurotransmitter release are predominantly studied in brain tissue or in neuronal cells isolated from embryonic mice, using a combination of electrophysiology and fluorescent imaging techniques. Transgenic animals are also bred to determine how these mechanisms are disrupted in disease. Professor Kirill Volynski’s team will expand on a new methodology recently developed by his collaborators at the University of Yale. The existing setup allows the reconstitution of single vesicle fusion under in vitro conditions. Kirill’s group will develop protocols to mimic in vitro the calcium signals that trigger vesicular release in live synapses. This will allow researchers to recapitulate synaptic architecture and physiology under cell-free conditions and enable mechanistic studies of calcium-evoked neurotransmitter release.

This award was made as part of the BBSRC/NC3Rs joint call for the development of next generation non-animal technologies (NATs).