Jon Martin Lindstrom, Ph.D.

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Emeritus Professor of Neuroscience
Department: Neuroscience

Contact information
130 John Morgan Bldg
3620 Hamilton Walk
Philadelphia, PA 19104-6074
Office: 215-573-2859
Fax: 215-573-2858
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.

Selected Publications

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 102: 158-73, Mar 2016.

Lucero LM, Weltzin MM, Eaton JB, Cooper JF, Lindstrom JM, Lukas RJ, Whiteaker P: Differential α4(+)/(-)β2 Agonist-binding Site Contributions to α4β2 Nicotinic Acetylcholine Receptor Function within and between Isoforms. Journal of Biological Chemistry 291(5): 2444-59, Jan 2016.

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(48): 28834-46, Nov 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.

Kusner L, Losen M, Vincent A, Lindstrom J, Tzartos S, Lazaridis 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.

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, Lazaridis 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.

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.

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Last updated: 09/28/2017
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