In my laboratory we study the chemical synapse, a specialized junction where neurons communicate with adjacent cells, such as sensory receptors, muscle cells, or other neurons. We are trying to understand how the presynaptic cell at a chemical synapse controls the release of its messenger molecule, the neurotransmitter, and how this process can be modified by synaptic activity. Since calcium ions have been clearly implicated in the initiation of neurotransmitter release, one of our goals is to learn more about how presynaptic nerve terminals regulate intracellular calcium. We have also studied how metabotropic acetylcholine receptors, nitric oxide, and endocannabinoids modifies the release of neurotransmitter; how synaptic vesicles, which package neurotransmitter molecules, are recycled back into the presynaptic cell following the release of neurotransmitter; and how glial cells (the "supporting" cells of the nervous system) are influenced by synaptic activity and, in turn, modulate the release of neurotransmitter. Current Working Model of the Vertebrate Neuromuscular Junction This model represents our current understanding of the signaling pathways involved in muscarine-induced synaptic depression at the vertebrate NMJ along with some speculation as to the pathways that may be involved in synaptic enhancement (the data supporting these latter speculations are not included on this poster). Block arrows represent the diffusion or transport of a signaling molecule. Curved block arrows indicate an enzymatic conversion. Solid black arrows depict steps that have been experimentally verified, whereas dashed arrows reveal steps that contain unknown details or hypothesized relationships. All chemicals in italics and their respective arrows are meant to show the targets of the experimental reagents used. We are not sure whether NO is produced in the muscle fibers or the PSCs so we have included each possibility and noted both with (*). NO, acting via PKG, is necessary but not sufficient to modulate neurotransmitter release and we have noted this with a dashed line and (&). We do not yet know the specific target of PKG. The presence of COX-2 in the muscle, the M1 influence on COX-2 and the mechanism of PGE2-G action are all based on preliminary data (not shown in this poster). Abbreviations: intracellular calcium transient (?[Ca2+]i), acetylcholine (ACh), nicotinic acetylcholine receptor (nAChR), muscarinic acetylcholine receptor subtype 3 (M3), G-protein (G), phosphatidylinositol or its phosphorylated derivatives (PI), phospholipase C (PLC), diacylglycerol (DAG), diacylglycerol lipase (DGL), 2-arachidonylglycerol (2-AG), cannabinoid receptor subtype 1 (CB1), nitric oxide synthase (NOS), nitric oxide (NO), guanosine triphosphate (GTP), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP), cGMP-dependant protein kinase (PKG), cyclooxygenase-2 (COX-2), prostaglandin E2 glycerol (PGE2-G). Most of our experiments are carried out on the specialized synapse between a motor nerve and muscle cell, called the neuromuscular junction. We study this synapse in several different animals, including frogs, crayfish and lizards, with the actual preparation used depending on the specific needs of the project. The techniques that we use include both intracellular and extracellular recording of electrical activity in the nerve and muscle. We also use optical methods to monitor various cellular parameters, such as intracellular calcium activity, pH, endocytosis, etc.
Clark A Lindgren
Patricia A. Johnson Professor of Neuroscience
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Education / Degrees:
B.S., Physics, Wheaton College M.S., Ph.D., Physiology, University of Wisconsin-Madison Postdoctorate, Neurobiology, Duke University
Biology 135: Structure and Function of Organisms Biology 150: Introduction to Biological Inquiry "The Language of Neurons" Biology 236: The Biology of Cells Biology 251: Molecules, Cells, and Organisms, with Lab Biology 363: Neurobiology, with Lab Biology 364: Animal Physiology, with Lab Neuroscience 250: Neuroscience Foundations, Future, & Fallacies, with Lab Tutorial: "Acrimony, Authority, and Assumptions" Tutorial: "150 Years Later: The Legacy of a Book"