Pre- and postsynaptic determinants of neurotransmitter release at individual release sites

Connections between neurons are made up of several individual release sites, each with a different probability of releasing a neurotransmitter upon arrival of an action potential. How pre- and postsynaptic neurons work in concert to regulate release probability (Pr) at different connection points is still unclear. A novel combination of techniques will be used to study Pr at individual active zones and to identify the mechanisms involved in its regulation.

We will test the hypothesis that Pr is regulated in concert by both pre- and postsynaptic compartments using electrophysiology, live fluorescence imaging and serial electron microscopy both at cortical boutons and at the Calyx of Held, a giant synapse in the auditory pathway. By labelling pre- or postsynaptic cortical neurons, we will ascertain whether the presynaptic origin as well as the target neuron play a key role in setting Pr at the cellular and network level. Using the Calyx of Held, where hundreds of active zones contact the same postsynaptic soma, will reduce confounding elements, such as compartmentalised postsynaptic activity.

This project will identify the mechanisms by which individual terminals embedded in a network set synaptic strength which will be useful for detection of synaptic changes and degeneration at an early stage.