We are interested in molecular and cellular aspects of synaptic transmission. Neurotransmitter release is controlled by the number of synaptic vesicles that are ready for fusion with the plasma membrane in response to calcium influx. Once this pool of vesicles is exhausted, it has to be replenished by vesicles from reserve pools or vesicles that have recently been recycled. The overall aim of our lab is to establish how the number of release-ready vesicles is regulated and what effect this and other pools of vesicles can have on synaptic transmission. We are following these ideas in several independent projects.

1. Vesicle pools at the ribbon synapse of frog vestibular hair cells.
We are investigating whether only vesicles that are interacting with the plasma membrane, i.e. that are docked, can fuse with fast kinetics. Using frog vestibular hair cells and cell membrane capacitance measurements, we find that in 25 milliseconds about 10 times more vesicles fuse that are docked to the membrane. We are now in the process of elucidating where these vesicles are coming from and how they can fuse with such fast kinetics. In particular we are following the hypothesis that multivesicuar release and compound fusion can occur at this synapse.
Frederick Gregory

2. Regulation of vesicle pools at hippocampal synapses.
We are using cultured hippocampal neurons and brain slices to ask whether particular molecules can regulate synaptic strength by modifying vesicular pools. We are especially focusing on short term plasticity such as paired-pulse depression/facilitation and responses to short trains of stimuli. We are overexpressing plasmids containing the coding sequence for the proteins of interest or anti-sense sequences.
Tanya Sippy

3. Timing of neurotransmitter release.
Multi-vesicular release events have been observed at different synapses. Typically, these events are characterized by a large amplitude with a remarkably smooth and fast rise-time, and little dispersion of the exact fusion time can be observed. We are exploring what molecules could be involved in synchronizing vesicle fusion events to each other. This is investigated by disrupting protein-protein interactions using peptides in cultured slices.
Alberto Cruz-Martín

4. Vesicle recycling and neurodegenerative disease.
Certain hereditary forms of neurodegenerative diseases are caused by mutations in proteins found at the presynaptic nerve terminal. Using cultured hippocampal and striatal neurons we are investigating how these proteins alter synaptic transmission.
Kristen Willeumier

5. Peptide regulation.
NPY is one of the most abundant neuropeptides in the brain. We are investigating how activation of particular NPY receptors in the hippocampus and in the retina alters synaptic transmission.
Iona D'Angelo