Miriam M. Salpeter

Professor

EM Autoradiogram of Lizard Endplate showing labeled acetylcholine receptors

Neurobiology and Behavior W113 Seeley G. Mudd Hall Cornell University Ithaca, NY 14853 USA Phone - Office: (607) 254-4341 Phone - Lab: (607) 254-4338 Fax: (607) 254-4308 Internet: mms13@cornell.edu Web Page: http://www.nbb.cornell.edu/ neurobio/salpeter/salpeter.html

Office hours: Contact Kathie Burdick at 254-4351

Courses Taught: Clinical Aspects of Neurobiology

Research Interests:

Our laboratory is concerned with the development and cellular organization of the nervous system. Areas of interest include synaptogenesis, trophic interactions between nerve and its innervated structures, and the relative roles of glia and neurons in neural function. A major emphasis is on events at the vertebrate neuromuscular junction (nmj) as a model synapse. We are interested in how and under what circumstances the synaptic molecules accumulate during development, what determines synaptic stability and how it can be modified, and finally, what are the physiological and behavioral consequences of the unique synaptic molecular organization. The vertebrate neuromuscular junction is a peripheral nicotinic cholinergic synapse with many unique properties that are under neural control. Recently, many studies have elucidated the organization, distribution, and properties of both the nicotinic acetylcholine receptors (AChR) and acetylcholine esterases (AChE) during development and in the adult nmj. It was found that during innervation of peripheral muscle radical changes occur in the localization and behavior of these molecules, especially of the AChR. Recent evidence indicates that molecular changes in AChR subunit composition may account for some developmental changes seen during synaptogenesis. Studies in our laboratory are aimed at understanding the molecular mechanisms involved, and the role played by the nerve in those events. Specifically, is the neural influence mediated by released chemical substances, neurally induced muscle activity, or a combination of those effects? Techniques employed are electron microscopy, both transmission and scanning electron-microscope autoradiography; electrophysiology; and in situ hybridization of specific messenger RNA and cDNA probes. We also study the physiological consequences of the molecular organization at the vertebrate nmj. Electron-microscope autoradiographic studies are combined with physiological studies, using voltage clamp, to assess the role played by the distribution of acetylcholine receptors and esterases in determining the time course of the miniature end-plate currents produced by the release of a single quantal packet of acetylcholine. From those studies we are deriving the kinetic parameters for acetylcholine diffusion in the cleft, its binding to acetylcholine receptors and esterases, and the subsequent receptor gating times.

Selected Publications:

Xu, R. and M.M. Salpeter 1999. Rate constants of acetylcholine receptor internalization and degradation in mouse muscles. J. Cellular Physiology 181:107-112.

Stiles, J.R., I. Kovyazina, E.E. Salpeter and M.M. Salpeter 1999. The temperature sensitivity of miniature endplate currents is mostly governed by channel gating: Evidence from optimized recordings and monte carlo simulations. Biophys. J. 77:1177-1187.

Salpeter, M.M. 1999. The constant junctions. Science (Perspectives) 286:424-425.

Xu, R. and M.M. Salpeter 1997. Acetylcholine receptors in innervated muscles of dystrophic mdx mice degrade after denervation. J. Neurosci. 17:8194-8200.