Jen-Wei Lin

My main research focus is on the biophysical events underlying transmitter release. Neurotransmitter secretion involves ion channel gating, diffusion and buffering of calcium ions, vesicular fusion as well as the mobilization and recycling of, synaptic vesicles. We use electrophysiological and imaging techniques to monitor processes underlying synaptic transmission at a high time resolution. Using the crayfish neuromuscular junction, we perform simultaneous pre- and post-synaptic recordings or voltage clamp to analyze the kinetics of transmitter release under control and facilitated conditions, and calcium sensitive dyes to monitor the dynamics of presynaptic calcium ion diffusion and buffering. We are currently focusing on mechanisms regulating the probability of transmitter release by comparing two classes of active zone residing in the same varicosity but with different release probabilities. Finally, since detailed events during the course of synaptic transmission happen at a sub-millisecond time scale and with nanometer spatial resolution, both of which are beyond the capability of current experimental techniques, we are using a mathematical modeling approach to gain insights to the behavior of calcium ions with sufficient resolution.

In addition to events occurring around the active zones, we also study the excitability of axonal branches to gain insights into the interaction between axonal excitability and transmitter release. We use voltage sensitive dyes to investigate action potentials and subthreshold activities in fine axonal branches. Recently, we have made two important advances in the study of axonal excitability. First, we can now place four electrodes in an axon simultaneously and investigate interactions between two different compartments. Second, we can now patch presynaptic varicosities. Our preliminary patch clamp findings suggest that crayfish terminals, unlike its main axonal trunk, are not excitable. Rather, terminal depolarization is mainly supported by forward charging current provided by proximal branches. These new findings suggest that axons at the crayfish opener neuromuscular junction is unique among axon-terminal model systems and can contribute to our understanding of axon-terminal excitability and synaptic transmission.