Dr. Wes Thompson
Office: PAT 302
phone: (512) 471-3031
lab: PAT 312
fax: 471-9651
email:
Wesley Thompson received his Ph.D. in molecular biology from the University of California, Berkeley in 1975. He then did postdoctoral work at the Institute of Physiology in Oslo, Norway and at the Department of Physiology and Biophysics at Washington University School of Medicine before joining the faculty at the University of Texas in 1979. Dr. Thompson is presently a professor in the Section of Neurobiology and a member of the Institute for Neuroscience and the Institute for Cell and Molecular Biology. He has been a Searle Scholar, a recipient of a Research Career Development Award from NIH, a fellow of the Institute for Cell and Molecular Biology, and a recipient of a teaching award from the College of Natural Sciences. He presently has a Javits Neuroscience Investigator Award from NIH. He serves on a study section to evaluate NIH grant applications and teaches in the summer in the Neurobiology course at the Marine Biological Institute at Woods Hole.
Research Interests
All neuroscientists agree that the brain functions by virtue of the way its neurons are wired together in intricate circuits. I study how these connections between neurons, i.e. synapses, are formed and maintained. I study the simplest of all vertebrate synapses, the neuromuscular junction (NMJ). This synapse, the connection between a motor neuron and a skeletal muscle fiber, offers a number of advantages for the types of questions that interest me. The synapse is huge, easily accessible, and easily manipulated. There is only a single “pre-synaptic” input and the target cell is very large. This is in contrast to most synapses in the central nervous system where the pre- and post-synaptic elements are very small and the numbers of synapses and cells closely packed together are enormous. There are a number of neurological disorders that affect the integrity of this synapse or its components.
The specific issue that I pursue is the role of the glial cells that are present at this synapse. At the NMJ there are several Schwann cells (the glial cells of the peripheral nervous system or PNS) that are in intimate contact with the terminal branches of each motor neuron. If a muscle is denervated by crushing the muscle nerve, the Schwann cells react to the degeneration of the axons and nerve terminals by growing long, elaborate processes that extend away from the synaptic site. Motor axons regenerate quite readily and Schwann cell processes serve as substrates for the regrowing axons. In this way, the Schwann cells apparently determine where in the muscle regenerating axons grow.
In my lab we image Schwann cells and axons in living mice to determine the relationships between axons and Schwann cells at normal NMJs as well as during reinnervation and sprouting. For this purpose, we have made transgenic mice in which green fluorescent protein (GFP) is expressed in Schwann cells. We have mated these animals to animals obtained from collaborators in which cyan fluorescent protein (CFP), is expressed in axons. In this way we produce mice bearing two transgenes. We can stain the acetylcholine receptors with small concentrations of a snake toxin, bungarotoxin, that is conjugated to a red fluorochrome, rhodamine. Thus, we can insert a microscope objective into a small lesion in the skin of a mouse and observe green Schwann cells, blue axons and axon terminals, and red acetylcholine receptors. Moreover, each site bears a “fingerprint” that one can easily use to identify this same synaptic site hours, days, weeks, months, or even years later. Thus, it is possible to identify the synaptic components at individual synapses and see how they change with time. We are investigating how motor neurons regenerate and sprout in the muscle in response to nerve injury. In this way, we are learning exactly the relationships between axons and their glial cells as synapses reform.
We are also examining and manipulating the molecules involved in this relationship between glia and nerve terminals. We have made transgenic mice in which a target gene in Schwann cells can be turned on at the will of the investigator by simply giving the mouse an oral antibiotic. The system works well and we are now embarking on experiments to express proteins that we believe are crucial for the function of these cells.
In summary, research in my lab uses imaging and mouse transgenic technology to explore mechanisms involved in synaptic maintenance and in repair of neuronal lesions.