Jon Martin Lindstrom

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The Trustee Professor in Neuroscience
Department: Neuroscience

Contact information
217 Stemmler Hall
36th & Hamilton Walk
Philadelphia, PA 19104-6074
Office: 215-573-2859
Fax: 215-573-2858
Graduate Group Affiliations
B.A. (Biology)
University of Illinois, 1967.
(Neurobiology Course)
Marine Biology Laboratory Woods Hole, Massachusetts, 1970.
Ph.D. (Biology)
University of California San Diego, California, 1971.
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Description of Research Expertise

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.

Monoclonal antibodies; affinity chromatography; cloning and expression of native and mutant cDNAs; electrophysiology, and ligand binding.

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.

Description of Itmat Expertise

Dr. Lindstrom is interested in developing a specific immunosuppressive therapy for myasthenia gravis.

We are also interested in developing a positive allosteric modulator for alpha 4 beta 2 alpha 5 nicotinic receptors for use in smoking cessation.

Selected Publications

Kusner L, Losen M, Vincent A, Lindstrom J, Tzartos S, Lazarides K, and Martinez-Martinez P: Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model - recommendations for methods and experimental designs. Experimental Neurology 270: 3-10, 2015.

Weltzin M, Cooper J, Lindstrom J, Lukas R, and Whiteaker P: Distinctive effects of nicotinic receptor intracellular loop mutations associated with nocturnal frontal lobe epilepsy. Neuropharmacology in press, 2015.

Wang J, Kuryatov A, Sriram A, Zhuang J, Kamenecka T, Kenny P, and Lindstrom J: An accessory agonist binding site promotes activation of alpha 4 beta 2* nicotinic acetylcholine receptors. Journal of Biological Chemistry 290: 13907-13918, 2015.

Wang J, Kuryatov A, Jin Z, Norleans J, Kamenecka T, Kenny P, and Lindstrom J: A novel alpha 2/alpha 4 subtype-selective positive allosteric modulator of nicotinic acetylcholine receptors acting from the C-tail of an alpha subunit. Journal of Biochemistry 290: in press, 2015.

Luo J and Lindstrom J: AChR-specific immunosuppressive therapy of myasthenia gravis. Biochemical Pharmacology 97: 609-619, 2015.

Shorey-Kendrick L, Ford M, Allen D, Kuryatov A, Lindstrom J, Wilhelm L, Grant K, and Spindel E: Nicotinic receptors in nonhuman primates: analysis of genetic and functional conservation with humans. Neuropharmacology 96: 263-273, 2015.

Hone A, McIntosh J, Azam L, Lindstrom J, Lucero L, Whiteaker P, Passas J, Blazquez J, and Albillos A: Alpha-Conotoxins identify the alpha 3 beta 4* subtype as the predominant nicotinic acetylcholine receptor expressed in human adrenal chromatin cells. Molecular Pharmacology 88: 881-893, 2015.

Losen M, Martinez-Martinez P, Molenaar P, Lazaridid K, Tzartos S, Brenner T, Duan R, Luo J, Lindstrom J, and Kusner L: Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica receptors - recommendations for methods and experimental designs. Experimental Neurology 270: 18-28, 2015.

Wang J, Kuryatov A, and Lindstrom J: Expression of cloned alpha 6* nicotinic acetylcholine receptors. Neuropharmacology 96: 194-204, 2015.

Hussman G, DeDominicis K, Turner J, Yasuda R, Klehm J, Siao Y, Richardson J, Sahibzada N, Wolfe B, Lindstrom J, Blendy J, and Kellar K: Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain. Journal of Neurochemistry 129: 721-731, 2014.

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Last updated: 11/18/2015
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