DOCSLIB.ORG

Primer on the Autonomic Nervous System This

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Primer on the Autonomic Nervous System This Primer on the Autonomic Nervous System This. Page Intentionally Left Blank Primer on the Autonomic Nervous System Editor in Chief David Robertson Vanderbilt University Editors Italo Biaggioni Vanderbilt University Geoffrey Burnstock Royal Free & University College London Phillip A. Low The Mayo Clinic AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Elsevier Academic Press 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald’s Road, London WC1X 8RR, UK This book is printed on acid-free paper. ᭺• Copyright © 2004, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://elsevier.com), by selecting “Customer Support” and then “Obtaining Permissions.” Library of Congress Cataloging-in-Publication Data Primer on the autonomic nervous system / editor in chief, David Robertson; editors, Italo Biaggioni, Geoffrey Burnstock, Phillip A. Low.—2nd ed. p. ; cm. Includes bibliographical references and index. ISBN 0-12-589762-6 1. Autonomic nervous system—Diseases. 2. Autonomic nervous system—Physiology. I. Robertson, David, 1947– [DNLM: 1. Autonomic Nervous System Diseases—physiopathology. 2. Autonomic Nervous System—physiology. WL 600 P953 2004] RC407.P75 2004 616.8¢56—dc22 2003070923 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN: 0-12-589762-6 For all information on all Academic Press publications visit our Web site at www.academicpress.com Printed in the United States of America 040506070809 987654321 Contents List of Contributors xix Noradrenaline Phenotype 9 Preface xxvii Control Mechanism of DBH Gene Expression Is Closely Related to Autonomic Nervous System Development 9 PART Cholinergic Phenotype and the Switch of Neurotransmitter I Phenotypes by the Target Cell Interactions 9 3. Milestones in Autonomic Research ANATOMY MAX R. BENNETT 1. Development of the Autonomic Receptors 12 Nervous System Classical Transmitters: The Discovery of Noradrenaline, Acetylcholine, and Their Receptors 12 CARYL E. HILL The Discovery of New Transmitters, Including Nucleotides, Peptides, and Nitric Oxide 12 Pathways and Fate of Neural Crest Cells 3 Varicosities 12 Factors Operating during Neural Crest Migration 3 Varicosities Shown to be the Source of Transmitters 12 Neurite Outgrowth and Target Contact 4 Varicosities Have the Capacity to Take Up Transmitters Factors Involved in Neurite Outgrowth and Neuronal After Their Release 12 Survival 5 Varicosities Possess Receptors That on Activation Modulate Synapse Formation and Neuronal Differentiation 5 Further Transmitter Release 13 Conclusions 5 Generation of Currents and Second Messengers on Receptor Activation After Transmitter Release from Varicosities 13 2. Mechanisms of Differentiation of Action Potentials, Initiated by the Generation of Junction Autonomic Neurons Potentials, Are Caused by the Influx of Calcium Ions 13 KWANG-SOO KIM Control of the Influx of Calcium Ions Is a Principal Means of Decreasing Blood Pressure 13 The Autonomic Nervous System Is Derived from Neural Crest Cells 6 PART Signaling Molecules Regulate the Developmental Processes of the Autonomic Nervous System 6 II Transcriptional Code Underlying the Development and Phenotypic Specification of the Autonomic PHARMACOLOGY Nervous System 7 Mash1 7 Phox2 Genes 7 4. Central Autonomic Control Gata3 8 EDUARDO E. BENARROCH Activator Protein 2 8 Other Transcriptional Factors 8 Anatomy of Central Autonomic Areas 17 Neurotransmitter Phenotypes of the Autonomic Forebrain 17 Nervous System 9 Levels of Integration of Central Autonomic Control 18 v vi Contents Bulbospinal Level 18 9. Dopamine Receptors Pontomesencephalic Level 18 AKI LAAKSO AND MARC G. CARON Forebrain Level 18 Structural and Functional Characteristics of 5. Peripheral Autonomic Nervous System Dopamine Receptors 39 Gene Structure 39 ROBERT W. HAMILL AND ROBERT E. SHAPIRO Receptor Structure 39 Signal Transduction 40 Sympathetic Nervous System 20 D1-like Receptors 40 Sympathoadrenal Axis and the Adrenal Gland 23 D2-like Receptors 41 Parasympathetic Nervous System 24 Oligomerization 41 The Concept of Plurichemical Transmission and Pharmacology 42 Chemical Coding 25 Distribution 42 Functional Neuroanatomy and Biochemical Distribution in the Brain 42 Pharmacology 27 D1 Receptors 42 D2 Receptors 42 D3 Receptors 42 6. The Autonomic Neuroeffector Junction D4 Receptors 43 GEOFFREY BURNSTOCK D5 Receptors 43 Dopamine Receptors in the Periphery 43 Structure of the Autonomic Neuromuscular Junction 29 Regulation 43 Varicose Terminal Axons 29 Junctional Cleft 29 Prejunctional and Postjunctional Specialization 30 10. Noradrenergic Neurotransmission Muscle Effector Bundles and Gap Junctions 30 DAVID S. GOLDSTEIN Autonomic Neurotransmission 30 Electrophysiology 30 Noradrenergic Innervation of the Cardiovascular Receptor Localization on Smooth Muscle Cells 31 System 44 Model of Autonomic Neuroeffector Junction 32 Norepinephrine: The Sympathetic Neurotransmitter 45 Norepinephrine Synthesis 45 7. Autonomic Neuromuscular Transmission Storage 46 Release 46 MAX R. BENNETT Disposition 47 New Transmitters and the Concept of Cotransmitters 34 Varicosities, Vesicle-Associated Proteins, and 11. a -Adrenergic Receptors Calcium Fluxes 34 1 Ionotropic Receptors Are Localized to the Muscle ROBERT M. GRAHAM Membrane at Varicosities 34 Subtypes 50 Metabotropic and Ionotropic Receptors Are Structure and Signaling 50 Internalized and Recycled after Binding Ligand Binding and Activation 50 Transmitter 34 Regulation 52 Sources of Intracellular Calcium in Smooth Muscle Vascular Subtypes 52 for Initiating Contraction 35 Modulation of Calcium Influx and the Control of Hypertension 35 12. a2-Adrenergic Receptors LEE E. LIMBIRD 8. Dopaminergic Neurotransmission CHRISTOPHER BELL 13. b-Adrenergic Receptors Transmitter Neurochemistry 36 STEPHEN B. LIGGETT Transmitter Synthesis 36 Transmitter Storage and Release 36 Signaling of b-AR Subtypes 57 Transmitter Recycling 36 Regulation of b-AR Function 57 Future Questions 37 Polymorphisms of b-AR 58 Contents vii 14. Purinergic Neurotransmission 18. Acetylcholinesterase and Its Inhibitors GEOFFREY BURNSTOCK ALBERT ENZ Sympathetic Nerves 61 Mechanism of Action 77 Parasympathetic Nerves 61 Acetylcholinesterase Inhibitors 77 Sensory-Motor Nerves 62 Pharmacologic Actions of Acetylcholinesterase Intramural (Intrinsic) Nerves 63 Inhibition 77 Skeletal Neuromuscular Junctions 63 Clinical Applications of Anticholinesterases 79 Synaptic Purinergic Transmission in Ganglia and Cholinesterase Inhibitors and Alzheimer’s Disease 80 Brain 64 Glial Cells 64 Plasticity of Expression of Purinergic Cotransmitters 64 Long-Term (Trophic) Signaling 64 19. Amino Acid Neurotransmission WILLIAM TALMAN P2X3 Receptors and Nociception 64 Future Developments 64 20. Peptidergic Neurotransmission 15. Adenosine Receptors and GRAHAM J. DOCKRAY Autonomic Regulation Families of Peptide Transmitters 83 ITALO BIAGGIONI Generic Features of Peptidergic Transmission 83 Biosynthesis 83 Postsynaptic Antiadrenergic Effects of Adenosine 66 Storage and Release 83 Presynaptic Effects of Adenosine on Efferent Nerves Receptors 84 and Ganglionic Transmission 66 Degradation 84 Adenosine and Central Autonomic Regulation 66 Chemical Coding 84 Neuroexcitatory Actions of Adenosine on Afferent Overview of Peptides in the Autonomic Nervous Pathways 67 System 84 Integrated View of Adenosine and Cardiovascular Autonomic Regulation 67 21. Leptin Signaling in the Central Nervous System 16. Acetylcholine and Muscarinic Receptors KAMAL RAHMOUNI, WILLIAM G. HAYNES, AND ALLYN L. MARK B. V. RAMA SASTRY AND DAVID ROBERTSON Central Neural Action of Leptin 86 Acetylcholine Synthesis and Metabolism: Drug Leptin Receptor 86 Mechanisms 70 Intracellular Mechanisms of Leptin Signaling 86 Acetylcholine Receptors 70 Site of Leptin Action in the Brain 87 Muscarinic Agonists 71 Interaction of Leptin and Neuropeptides in the Muscarinic Autonomic Effects of Acetylcholine 71 Hypothalamus 87 Muscarinic Antagonists 72 Neuropeptide Y 87 Melanocortin System 88 Other Mediators 88 Conclusion 89 17. Nicotinic Acetylcholine Receptors: Structure and Functional Properties PALMER TAYLOR 22. Nitrergic Neurotransmission JILL LINCOLN Structural Considerations 73 Subtype Diversity of Nicotinic Receptors 73 Synthesis of Nitric Oxide 90 Electrophysiologic Events Associated with Receptor Mechanisms of Nitrergic Neurotransmission 90 Activation 74 Nitrergic Neurotransmission in the Autonomic Nervous Distribution of Nicotinic Receptors 76 System and Pathologic Implications 91 viii Contents 23. Serotonin Receptors and 29. Gastrointestinal Function Neurotransmission MICHAEL CAMILLERI ELAINE SANDERS-BUSH AND CHARLES D. NICHOLS Salivary Secretion 118 Localization 93 Gastric Secretion 118 Synthesis and Metabolism 93 Pancreaticobiliary Secretion 118 Neurotransmission 93 Bile 118 Receptors 94 Intestinal Secretion and Absorption 119 Pharmacology and Role in Disease 94 Control of Gut Motility 119 Normal Gastrointestinal Motor Function
Load more

Recommended publications
  • Communication Center
    2/16/2012 Communication Center Nervous System Regulation •The Neural System is only 3% of your body weight, but is the most complex organ system. •Nervous impulses are fast acting (milliseconds) Neural vs. Hormonal but short lived. Overview •The nervous system includes all neural tissue in the body. Basic units are: Two Anatomical Divisions of The Nervous System a. Neurons (individual nerve cells) 1. CNS: Central Nervous System b. Neuroglia • supporting cells • Brain & Spinal Cord • separate & protect the neurons • Responsible for integrating, processing, & • provide supporting framework coordinatinggy sensory data and motor commands. i.e.- stumble example • act as phagocytes • regulate composition of interstitial fluid • The brain is also the organ responsible for • a.k.a. glial cells intelligence, memory, learning, & emotion • outnumber neurons 1 2/16/2012 2. PNS: Peripheral Nervous System PNS has 2 functional divisions • All nervous tissue outside CNS Afferent Division (Sensory) • Carries sensory data to CNS, carries motor •Bring sensory information to CNS from receptors in commands from the CNS. peripheral nervous tissue & organs. • Bundles of nerve fibers carry impulses in the PNS are known as per ip hera l nerves or jus t “nerves”. Efferent Division (Motor) •Carries motor commands from CNS to muscles & • Nerves attached to the brain are called cranial glands, these target organs are called effectors. nerves. Nerves attached to the spinal cord are called spinal nerves. The Efferent Division is broken into Somatic & The ANS has a: Autonomic Components (SNS) Somatic System: controls skeletal muscle contractions these can be voluntary (conscious) or sympathetic division involuntary (unconscious) {reflexes}. } antagonistic effects parasympathetic (ANS) Au tonom ic Sys tem: * a.k.a.
    [Show full text]
  • The Noradrenaline Transporter As Site of Action for the Anti-Parkinson Drug Amantadine
    Neuropharmacology 62 (2012) 1708e1716 Contents lists available at SciVerse ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm The noradrenaline transporter as site of action for the anti-Parkinson drug amantadine Christian Sommerauer a, Patrick Rebernik a, Harald Reither a, Christian Nanoff b, Christian Pifl a,* a Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria b Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Wahringerstrasse 13a, A-1090 Vienna, Austria article info abstract Article history: Amantadine is an established antiparkinsonian drug with a still unclear molecular site of action. In vivo Received 5 September 2011 studies on rodents, in vitro studies on tissue of rodents as well as binding studies on post mortem human Received in revised form tissue implicate monoamine transporters and NMDA receptors. In order to re-examine its action at 17 November 2011 human variants of these proteins on intact cells we established cells stably expressing the human NR1/2A Accepted 28 November 2011 NMDA-receptor, noradrenaline transporter (NAT) or dopamine transporter (DAT) and tested the activity of amantadine in patch-clamp, uptake, release, and cytotoxicity experiments. Amantadine was less Keywords: potent in blockade of NMDA-induced inward currents than in blockade of noradrenaline uptake and in Amantadine Noradrenaline transporter induction of inward currents in NAT expressing cells. It was 30 times more potent in blocking uptake in e m Carrier-mediated release NAT- than in DAT cells. Amantadine induced NAT-mediated release at concentrations of 10 100 Min Transport-related currents superfusion experiments and blocked NAT-mediated cytotoxicity of the parkinsonism inducing neuro- þ NMDA-receptor toxin 1-methyl-4-phenyl-pyridinium (MPP ) at concentrations of 30e300 mM, whereas 300e1000 mM Parkinson’s disease amantadine was necessary to block NMDA-receptor mediated cytotoxicity.
    [Show full text]
  • P2 Receptor-Mediated Modulation of Neurotransmitter Release—An Update
    Purinergic Signalling (2007) 3:269–284 DOI 10.1007/s11302-007-9080-0 ORIGINAL ARTICLE P2 receptor-mediated modulation of neurotransmitter release—an update Beáta Sperlágh & Attila Heinrich & Cecilia Csölle Received: 13 July 2007 /Accepted: 28 August 2007 / Published online: 9 October 2007 # Springer Science + Business Media B.V. 2007 Abstract Presynaptic nerve terminals are equipped with a ENPP ectonucleotide pyrophosphatase number of presynaptic auto- and heteroreceptors, including EJP excitatory junction potential ionotropic P2X and metabotropic P2Y receptors. P2 recep- ENTPDase ectonucleoside triphosphate diphosphohydro- tors serve as modulation sites of transmitter release by ATP lase and other nucleotides released by neuronal activity and EPP end plate potential pathological signals. A wide variety of P2X and P2Y EPSC excitatory postsynaptic current receptors expressed at pre- and postsynaptic sites as well as EPSP excitatory postsynaptic potential in glial cells are involved directly or indirectly in the GABA +-aminobutyric acid modulation of neurotransmitter release. Nucleotides are GPCR G-protein coupled receptor released from synaptic and nonsynaptic sites throughout the IL-1β interleukin-1β nervous system and might reach concentrations high enough IPSC inhibitory postsynaptic current to activate these receptors. By providing a fine-tuning LC locus coeruleus mechanism these receptors also offer attractive sites for LPS lipopolysaccharide pharmacotherapy in nervous system diseases. Here we mEPP miniature EPP review the rapidly emerging data on the modulation of mEPSC miniature EPSC transmitter release by facilitatory and inhibitory P2 receptors NA noradrenaline and the receptor subtypes involved in these interactions. NMJ neuromuscular junction NT neurotransmitter Keywords Neuromodulation . Presynaptic . P2X receptor . NTS nucleus tractus solitarii P2Y receptors .
    [Show full text]
  • Qt9vp7s85t.Pdf
    UC Irvine UC Irvine Previously Published Works Title Modulation of anxiety through blockade of anandamide hydrolysis. Permalink https://escholarship.org/uc/item/9vp7s85t Journal Nature medicine, 9(1) ISSN 1078-8956 Authors Kathuria, Satish Gaetani, Silvana Fegley, Darren et al. Publication Date 2003 DOI 10.1038/nm803 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California ARTICLES Modulation of anxiety through blockade of anandamide hydrolysis SATISH KATHURIA1, SILVANA GAETANI1, DARREN FEGLEY1, FERNANDO VALIÑO1, ANDREA DURANTI2, ANDREA TONTINI2, MARCO MOR3, GIORGIO TARZIA2, GIOVANNA LA RANA4, ANTONIO CALIGNANO4, ARCANGELA GIUSTINO5, MARIA TATTOLI5, MAURA PALMERY6, VINCENZO CUOMO6 & DANIELE PIOMELLI1 1Department of Pharmacology, University of California, Irvine, California, USA 2Institute of Medicinal Chemistry, University of Urbino, Urbino, Italy 3Pharmaceutical Department, University of Parma, Parma, Italy 4Department of Experimental Pharmacology, University of Naples, Naples, Italy 5Department of Pharmacology and Human Physiology, University of Bari, Bari, Italy 6Department of Pharmacology and General Physiology, University of Rome “La Sapienza”, Rome, Italy Correspondence should be addressed to D.P.; e-mail: [email protected] Published online 2 December 2002; doi:10.1038/nm803 The psychoactive constituent of cannabis, ∆9-tetrahydrocannabinol, produces in humans subjec- tive responses mediated by CB1 cannabinoid receptors, indicating that endogenous cannabi- noids may contribute to the control of emotion. But the variable effects of ∆9-tetrahydrocannabinol obscure the interpretation of these results and limit the therapeutic po- tential of direct cannabinoid agonists. An alternative approach may be to develop drugs that am- plify the effects of endogenous cannabinoids by preventing their inactivation.
    [Show full text]
  • Properties of the Venous and Arterial Innervation in the Mesentery
    J. Smooth Muscle Res. (2003) 39 (6): 269–279 269 Invited Review Properties of the Venous and Arterial Innervation in the Mesentery David L. KREULEN1 1Department of Physiology, Michigan State University, East Lansing, MI 48824-3320, USA Introduction The neural control of arteries and veins involves interactions between several vasoactive neurotransmitters released from the postganglionic sympathetic nerves and spinal sensory nerves. Sympathetic nerves are primarily vasoconstrictor in their action while the sensory nerves are vasodilatory; a result of the neurotransmitters released by these nerves. Thus, the nervous regulation of the vascular component of systemic blood pressure and of regional blood flow is the summation of vasoconstrictor and vasodilatory influences. Also, although the influence of arterial diameter on systemic blood pressure has received the most attention, venous diameter and compliance also are important in the regulation of blood pressure. The nervous regulation of blood flow and blood pressure depends upon the organization of sensory and sympathetic pathways to the vasculature as well as the events at the neuro-effector junctions in artery and vein. The sympathetic and sensory innervation of the mesenteric circulation consists of prevertebral sympathetic ganglion and dorsal root ganglion neurons, respectively. The axons of the neurons travel to the mesenteric arteries and veins in the paravascular nerves, which divide in the adventitia of the blood vessels to form the perivascular nerve plexus. Ultimately these axons divide into terminal axons, lose their Schwann cell sheath, and form neuroeffector junctions with vascular smooth muscle cells (Klemm et al., 1993). Although we know that arteries and veins are innervated by separate sympathetic neurons, all the mechanisms whereby these separate innervations regulate systemic blood pressure are not known.
    [Show full text]
  • Neuron Types and Neurotransmitters
    Neuron types and Neurotransmitters Faisal I. Mohammed. PhD, MD University of Jordan 1 Objectives Understand synaptic transmission List types of sensory neurons Classify neurotransmitters Explain the mechanism of neurotransmission Judge the types of receptors for the neurotrasmitters University of Jordan 2 Functional Unit (Neuron) 3 Transmission of Receptor Information to the Brain ➢The larger the nerve fiber diameter the faster the rate of transmission of the signal ➢Velocity of transmission can be as fast as 120 m/sec or as slow as 0.5 m/sec ➢Nerve fiber classification ➢type A - myelinated fibers of varying sizes, generally fast transmission speed ➢subdivided into a, b, g, d type B- partially myelinated neurons (3-14m/sec speed) ➢type C - unmyelinated fibers, small with slow transmission speed University of Jordan 4 Types of Nerve Fiber -Myelinated fibers – Type A (types I, II and III) - A α - A β - A γ - A δ -Umyelinated Fibers- Type C (type IV) University of Jordan 5 Neuron Classification University of Jordan 6 Structural Classification of Neurons University of Jordan 7 Neurotransmitters ❖Chemical substances that function as synaptic transmitters 1. Small molecules which act as rapidly acting transmitters ❖acetylcholine, norepinephrine, dopamine, serotonin, GABA, glycine, glutamate, NO 2. Neuropeptides (Neuromodulators) ❖more potent than small molecule transmitters, cause more prolonged actions ❖endorphins, enkephalins, VIP, ect. ❖hypothalamic releasing hormones ❖TRH, LHRH, ect. ❖pituitary peptides ❖ACTH, prolactin, vasopressin,
    [Show full text]
  • Shifting Gears: Liver SR-BI Drives Reverse Cholesterol Transport in Macrophages
    Shifting gears: liver SR-BI drives reverse cholesterol transport in macrophages Astrid E. van der Velde, Albert K. Groen J Clin Invest. 2005;115(10):2699-2701. https://doi.org/10.1172/JCI26241. Commentary Cholesterol efflux from macrophages, the first step in reverse cholesterol transport (RCT), is assumed to play a critical role in the pathogenesis of atherosclerosis. However, in vivo proof supporting this hypothesis is lacking, due to difficulties in determining the activity of this first step in RCT. In this issue of the JCI, Zhang et al. apply their recently developed method for measuring RCT in vivo to estimate RCT in mouse models with varying levels of HDL turnover. A surprisingly efficient clearance of cholesterol to feces is observed in mice overexpressing hepatic scavenger receptor class B type I (SR-BI), whereas in SR-BI–knockout mice, cholesterol clearance is diminished. The study demonstrates that hepatic SR- BI is a positive regulator of macrophage RCT in vivo. Find the latest version: https://jci.me/26241/pdf commentaries 1. Saitz, R. 2005. Clinical practice. Unhealthy alcohol 12. Willinger, U., et al. 2002. Anxiety as a predictor of 22. Valdez, G., and Koob, G. 2004. Allostasis and dys- use. N. Engl. J. Med. 352:596–607. relapse in detoxified alcohol-dependent patients. regulation of corticotropin-releasing factor and 2. Grant, B.F. 1994. Alcohol consumption, alcohol Alcohol Alcohol. 37:609–612. neuropeptide Y systems: implications for the devel- abuse and alcohol dependence. The United States 13. Pandey, S.C., Zhang, H., Roy, A., and Xu, T. 2005. opment of alcoholism.
    [Show full text]
  • Modulation of NMDA Receptor Activity During Physiological and Pathophysiological Events Christine Marie Emnett Washington University in St
    Washington University in St. Louis Washington University Open Scholarship Arts & Sciences Electronic Theses and Dissertations Arts & Sciences Winter 12-15-2014 Modulation of NMDA Receptor Activity During Physiological and Pathophysiological Events Christine Marie Emnett Washington University in St. Louis Follow this and additional works at: https://openscholarship.wustl.edu/art_sci_etds Part of the Biology Commons Recommended Citation Emnett, Christine Marie, "Modulation of NMDA Receptor Activity During Physiological and Pathophysiological Events" (2014). Arts & Sciences Electronic Theses and Dissertations. 347. https://openscholarship.wustl.edu/art_sci_etds/347 This Dissertation is brought to you for free and open access by the Arts & Sciences at Washington University Open Scholarship. It has been accepted for inclusion in Arts & Sciences Electronic Theses and Dissertations by an authorized administrator of Washington University Open Scholarship. For more information, please contact [email protected]. WASHINGTON UNIVERSITY IN ST. LOUIS Division of Biology and Biomedical Sciences Neurosciences Dissertation Examination Committee: Steven Mennerick, Chair James Huettner Daniel Kerschensteiner Peter D. Lukasiewicz Joseph Henry Steinbach Modulation of NMDA Receptor Activity During Physiological and Pathophysiological Events by Christine Marie Emnett A dissertation presented to the Graduate School of Arts and Sciences of Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy December 2014
    [Show full text]
  • Identity of Endogenous NMDAR Glycine Site Agonist in Amygdala Is Determined by Synaptic Activity Level
    ARTICLE Received 23 Jan 2013 | Accepted 21 Mar 2013 | Published 23 Apr 2013 DOI: 10.1038/ncomms2779 Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level Yan Li 1, Silvia Sacchi2, Loredano Pollegioni2, Alo C. Basu1, Joseph T. Coyle1 & Vadim Y. Bolshakov1 Mechanisms of N-methyl-D-aspartate receptor-dependent synaptic plasticity contribute to the acquisition and retention of conditioned fear memory. However, synaptic rules which may determine the extent of N-methyl-D-aspartate receptor activation in the amygdala, a key structure implicated in fear learning, remain unknown. Here we show that the identity of the N-methyl-D-aspartate receptor glycine site agonist at synapses in the lateral nucleus of the amygdala may depend on the level of synaptic activation. Tonic activation of N-methyl- D-aspartate receptors at synapses in the amygdala under low activity conditions is supported by ambient D-serine, whereas glycine may be released from astrocytes in response to afferent impulses. The release of glycine may decode the increases in afferent activity levels into enhanced N-methyl-D-aspartate receptor-mediated synaptic events, serving an essential function in the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation in fear conditioning pathways. 1 Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA. 2 Department of Biotechnology and Molecular Sciences, University of Insubria, ‘The Protein Factory’ Research Center for Protein Biotechnologies, Politecnico di Milano and University of Insubria, Varese 21100, Italy. Correspondence and requests for materials should be addressed to V.Y.B. (email: [email protected]).
    [Show full text]
  • Targeting Maladaptive Plasticity After Spinal Cord Injury to Prevent the Development of Autonomic Dysreflexia
    University of Kentucky UKnowledge Theses and Dissertations--Physiology Physiology 2019 TARGETING MALADAPTIVE PLASTICITY AFTER SPINAL CORD INJURY TO PREVENT THE DEVELOPMENT OF AUTONOMIC DYSREFLEXIA Khalid C. Eldahan University of Kentucky, [email protected] Author ORCID Identifier: https://orcid.org/0000-0003-1674-2386 Digital Object Identifier: https://doi.org/10.13023/etd.2019.064 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Eldahan, Khalid C., "TARGETING MALADAPTIVE PLASTICITY AFTER SPINAL CORD INJURY TO PREVENT THE DEVELOPMENT OF AUTONOMIC DYSREFLEXIA" (2019). Theses and Dissertations--Physiology. 41. https://uknowledge.uky.edu/physiology_etds/41 This Doctoral Dissertation is brought to you for free and open access by the Physiology at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Physiology by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known.
    [Show full text]
  • The Role of Norepinephrine in the Pharmacology of 3,4
    !"#$%&'#$&($)&*#+,-#+"*,-#$,-$."#$/"0*102&'&34$&($ 56789#."4'#-#:,&;41#."01+"#.01,-#$<9=9>6$?#[email protected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`,E#-E$ I0--$ D-.#*$ 2*#0.,J#2&11&-@X&*3a',2#-2#@aY48-28 -:aSX]a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
    [Show full text]
  • The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction
    Journal of Cardiovascular Development and Disease Review The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction Laura Fedele * and Thomas Brand * Developmental Dynamics, National Heart and Lung Institute (NHLI), Imperial College, London W12 0NN, UK * Correspondence: [email protected] (L.F.); [email protected] (T.B.); Tel.: +44-(0)-207-594-6531 (L.F.); +44-(0)-207-594-8744 (T.B.) Received: 17 August 2020; Accepted: 20 November 2020; Published: 24 November 2020 Abstract: The cardiac autonomic nervous system (CANS) plays a key role for the regulation of cardiac activity with its dysregulation being involved in various heart diseases, such as cardiac arrhythmias. The CANS comprises the extrinsic and intrinsic innervation of the heart. The intrinsic cardiac nervous system (ICNS) includes the network of the intracardiac ganglia and interconnecting neurons. The cardiac ganglia contribute to the tight modulation of cardiac electrophysiology, working as a local hub integrating the inputs of the extrinsic innervation and the ICNS. A better understanding of the role of the ICNS for the modulation of the cardiac conduction system will be crucial for targeted therapies of various arrhythmias. We describe the embryonic development, anatomy, and physiology of the ICNS. By correlating the topography of the intracardiac neurons with what is known regarding their biophysical and neurochemical properties, we outline their physiological role in the control of pacemaker activity of the sinoatrial and atrioventricular nodes. We conclude by highlighting cardiac disorders with a putative involvement of the ICNS and outline open questions that need to be addressed in order to better understand the physiology and pathophysiology of the ICNS.
    [Show full text]