Determining the role of activity-dependent bulk endocytosis via new molecules

Brain cells (neurones) communicate by releasing chemical neurotransmitters from small compartments called synaptic vesicles (SVs). The maintenance of neurotransmitter release is dependent on SVs being reformed by a process called endocytosis. There are different mechanisms of endocytosis and during very high brain activity the dominant mechanism is activity-dependent bulk endocytosis (ADBE). A number of essential processes are triggered by high brain activity, such as generation of learning and memory, suggesting ADBE will be an important mechanism in these events. However, research in this direction has been hindered by the absence of identified molecules that are specific to ADBE.

We propose to discover new ADBE-specific players, determine how they work and then disrupt their normal function to discover how ADBE controls neurotransmitter release, brain communication and animal behaviour. We have a series of candidate ADBE molecules to investigate.

This work will reveal how neurones communicate during high brain activity and how this communication could be altered by manipulating ADBE. It has the potential to allow a specific and selective intervention to modulate brain communication in healthy people or restore normal function in people with neurological disease.