Jon M. Lindstrom, Ph.D.

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				Jon M. Lindstrom, Ph.D. Trustee Professor of Neuroscience Department of Neuroscience School of Medicine 217 Stemmler Hall/6074 215-573-2859 Fax: 215-573-2858 E-mail: jslkk@mail.med.upenn.edu Click here for selected publications since Dr. Lindstrom's arrival at Penn RESEARCH INTERESTS The structure and function of nicotinic acetylcholine receptors. The autoimmune response to nicotinic receptors which causes myasthenia gravis: what initiates it, the pathological mechanisms by which it impairs neurosmuscular transmission, and how to specifically suppress it. The mechanisms of the differing effects of nicotine on the many subtypes of receptor: activation, desensitization, channel block, increased synthesis, and decreased turnover. The physiological roles of nicotinic receptors in development of specific synaptic connections, synaptic plasticity in learning and memory, and non-neuronal tissues. The pathological roles of nicotinic receptors in myasthenia, dysautonomia, epilepsy, myopia, Alzheimer's disease, and addiction to tobacco. RESEARCH TECHNIQUES Monoclonal antibodies; affinity chromatography; cloning and expression of native and mutant cDNAs; electrophysiology, and ligand binding. RESEARCH SUMMARY We are studying the biochemical and antigenic structure of nicotinic receptors from human muscle and Torpedo electric organ. We investigate pathological mechanisms and specific immunosuppressive therapy of experimental autoimmune myasthenia gravis in rats induced by immunization with purified receptor. We are also studying the structure and function of neuronal nicotinic receptors. These studies primarily involve expression of cloned human receptors in Xenopus oocytes and permanently transfected cell lines. We are also studying the effects of acute and chronic exposure to nicotine on various subtypes of nicotinic receptors. Understanding these effects is important for explaining both the effects of nicotine in tobacco and the effects of nicotinic drugs which are being developed. These structures should also reveal mechanisms through which nicotinic receptors could influence development and synaptic plasticity. Receptors are normally exposed to acetylcholine for milliseconds, but can be exposed to nicotine for hours. Nicotine, like any agonist, initially activates and then desensitizes receptors. On prolonged exposure it increases assembly of receptor subunits and decreases turnover of receptors in the surface membrane. It can be a full or partial agonist and block the cation channel. All of these effects vary depending on the receptor subtype. Combinations of these effects on various receptor subtypes in various regions are responsible for addiction to nicotine, tolerance to some of its effects, and mediating its many effects, which range from enhanced cognition to reduced anxiety and pain. KEY WORDS: Acetylcholine receptors; myasthenia gravis; nicotine