Department of Physiology and Biophysics
Professor of Physiology
My research is aimed at determining how nerve cells establish appropriate connections during the development of the nervous system. In recent years, my work has focused on the role of glutamate receptors in the development and regeneration of connections between the spinal cord and the muscle at the neuromuscular junction. Under normal conditions, each muscle fiber is innervated by a single nerve fiber, and Dr. Kirk Personius and I have recently begun to clarify the fact that glutamate receptors are integral to this process. Until our work, this transmitter system had never been examined as a contributing factor. We now are exploring the mechanisms by which glutamate influences these important events.
For many years prior to this work, I studied related questions in a very different systems. My work focused on how early visual input influences the formation of topographic binocular connections in the midbrain optic tectum of the frog, Xenopus laevis. The relay for visual input from each eye to the ipsilateral tectum, is a tegmental structure called the nucleus isthmi. The axons from this structure are guided to the optic tectum by unknown non-visual processes, but within the tectum, their final connections are completely dependent on the visual input coming from the 2 eyes. Only if both eyes are open, optically normal and exposed simultaneously to patterned input, will the isthomotectal projection form a map of the ipsilateral eye‘s field which is in proper topographic registration with the contralateral eye‘s field. Absence of visual input during development prevents the isthmic axons from terminating in a topographically organized way, and strabismus causes the isthmic axons to form an orderly but abnormal map which is in register with the map from the misaligned eye. The NMDA (N-methyl-D-aspartate) glutamate receptor is essential to this process, and the transmitters acetylcholine and GABA also are being investigated for their roles in control of plasticity.
The techniques that have been used in these experiments include extracellular electrophysiological recording methods, immunocytochemistry, electron microscopy, calcium imaging, receptor binding, whole-cell patch-clamping, knockdown techniques to control activation of transmitter systems, and anatomical tracing methods.