jenwelin@bu.edu

Cell and Molecular Neurobiology

Associate Professor of Biology
Ph.D., SUNY-Buffalo, 1986

Electrophysiology and molecular mechanisms of secretion

My main research focus is on the molecular and biophysical events underlying transmitter release in presynaptic terminals. Transmitter secretion is a complicated process that involves ion channel gating, the diffusion and buffering of calcium ions, and finally, vesicular fusion. In addition, the mobilization and recycling of synaptic vesicles are needed to maintain the function of a synapse and to contribute to the plasticity of synaptic transmission. From a physiological point of view, a quantitative description of the kinetic behavior of the transmitter release process is needed. At the same time, recent molecular biology studies have shown us that more than 50 proteins are specifically localized in presynaptic terminals, presumably to ensure that the process of synaptic transmission operates smoothly and to endow it with all its plasticity and complexity. Therefore, a complete understanding of the secretory events requires a combination of these two perspectives, i.e. establishment of a kinetic scheme for this multi-step process, along with rate constants for each step, together with identification of the molecules involved at each step.

At present, our kinetic analyses involve electrophysiological and imaging experiments at a high time resolution. Using the crayfish neuromuscular junction, we perform simultaneous pre- and postsynaptic recordings or voltage clamps to analyze the kinetic behavior of this synapse quantitatively. We also use a presynaptic electrode to pressure inject calcium sensitive dyes to monitor the dynamics of presynaptic calcium ion diffusion and buffering. In addition to measuring these biophysical parameters, we are also using uncaging techniques to raise intracellular calcium to a desired level with precise timing. The manipulation and measurement of these biophysical parameters is an essential part of our research program. Finally, detailed events during the course of synaptic transmission happen at a sub-millisecond time scale and nanometer spatial resolution, which is beyond the capability of current experimental techniques. Therefore, a mathematical modeling approach is also being used to gain insights to the behavior of calcium ions at such high time, and fine spatial, resolution. (The mathematical modeling is being carried out in collaboration with Dr. Victor Matveev at NIH).

To address molecular aspects of synaptic transmission, we have begun to work on the neuromuscular junction of Drosophila. We are now able to use a macropatch technique to measure transmitter release kinetics with a sub-millisecond time resolution. In addition, we are able to image presynaptic calcium dynamics at the fly neuromuscular junction. Application of the uncaging technique to the fly preparation is currently underway. We plan to select interesting mutants, with the help of our fly genetists friends, and apply the biophysical techniques described above to quantitatively analyze the kinetics of the release process in mutants.

In summary, our technical approach to the understanding of synaptic transmission is primarily biophysical, while our conceptual approach to the subject incorporates molecular perspectives.

Lin, J.-W., Fu, Q. and Allana, T. (2005) Probing the endogenous Ca2+ buffers at the presynaptic terminals of the crayfish neuromuscular junction. J. Neurophysiol. 94:377-386.

Lin, J.-W. and Fu, Q. 2005. Modulation of available vesicles and release kinetics at the inhibitor of the crayfish neuromuscular junction. Neuroscience 130 889=895.

Allana, T. N., Lin, J.-W. 2004. Relative distribution of Ca2+ channels at the crayfish inhibitory neuromuscular junction. J Neurophysiol. 92:1491-1500.

Lin, J.-W. and Faber, D. S. 2002. Modulation of synaptic delay during synaptic plasticity. Trends in Neurosciences, 25: 449-455.

Vyshedskiy, A., Allana , T. and Lin, J.W. 2000. Analysis of presynaptic Ca2+ influx and transmitter release kinetics during facilitation at the inhibitor of the crayfish neuromuscular junction. J. Neuroscience 20:6326-6332

Vyshedskiy, A. and Lin, J.-W. 2000. Presynaptic calcium influx at the inhibitor of the crayfish neuromuscular junction: An photometric study at a high time resolution. J. Neurophysiology 83:552-562

Vyshedskiy, A., Delaney K. and Lin, J.-W. 1998. Neuromodulators enhance transmitter release by two separate mechanisms at the inhibitor of crayfish opener muscle. J. Neuroscience 18:5160-5169

Kirillova, V. and Lin, J.-W. 1998. A whole-cell clamp study of dendrodendritic synaptic activities in mitral cells of turtle olfactory bulb slices. Neuroscience 87:255-264.

Vyshedskiy, A. and Lin, J.-W. 1997. A change of transmitter release kinetics during facilitation revealed by prolonged test pulses at the inhibitory synapse of the crayfish opener muscle. Journal of Neurophysiology 78:1791-1799.

Vyshedskiy, A. and J-W Lin. 1997. Activation and detection of the facilitation as studied by presynaptic voltage control at the inhibitor of the crayfish opener muscle. Journal of Neurophysiology 77(5):2300-2315.

Vyshedskiy, A. and J-W Lin. 1997. A study of the inhibitor of the crayfish neuromuscular junction by presynaptic voltage control. Journal of Neurophysiology 77(1):103-115.

Lin, J.-W. and R. Llinas. 1993. Depolarization activated potentiation of the T-fiber synapse in the blue crab. Journal of General Physiology 101:45-65.

Lin, J-W, B. Rudy, and R.R. Llinas. 1990. Funnel-web spider venom and a toxin fraction block calcium current expressed rat brain mRNA in Xenopus oocytes. Proceedings of the National Academy of Sciences, USA 87:4538-4542.

Lin, J-W., M. Sugimori, R.R. Llinas, T.L. McGuinness, and P. Greengard. 1990. Effect of synapsin I and calcium/calmodulin-dependent protein kinase II on spontaneous neurotransmitter release in the squid giant synapse. Proceedings of the National Academy of Sciences, USA 87:8257-8261.

Questions and comments are always welcome.
Copyright © 1996, The Trustees of Boston University
This document was last modified on September 20, 2005.