Synaptic Transmission

Description

Synaptic transmission is the process by which neurons communicate with one another at synapses, which is essential for normal function of the central and peripheral nervous systems. Synaptic dysfunction is linked to a number of conditions affecting the nervous system, including schizophrenia, Alzheimer’s disease, Parkinson’s disease, impairments in muscle control, and other neurological disorders. Synaptic Transmission is a comprehensive guide to the topic of neurotransmission, providing an in-depth discussion of many aspects of synapse structure and function, a fundamental part of the neuroscience discipline. Chapters include boxes that describe renowned/award-winning researchers and their contributions to the field of synaptic transmission, diseases relevant to the material presented, details of experimental approaches used to study synaptic transmission, and interesting asides that expand on the topics covered. This book will inspire students to appreciate how the basic cellular and molecular biology of the synapse can lead to a better understanding of nervous system function and neurological disorders, training future researchers and clinicians in this critical discipline. A comprehensive reference on synaptic structure, physiology, function, and neurotransmissionDiscusses many landmark experiments in the field of synaptic transmission to emphasize core principlesChapters include references to primary scientific literature, relevant review articles, and books, many of which could be assigned as discussion material for courses focused on this topic Cover Synaptic Transmission Copyright Preface Acknowledgments 1 Introduction Hypothesis Development The Use of Animal Model Systems to Study Synapses References Part I: Synaptic Biophysics and Nerve Terminal Structure 2 The Formation and Structure of Synapses How Do Neurons Send Signals to One Another? Synapse Structure and Organization How Does the Neuron Assemble the Cellular Components Required to Create Synapses? Construction of Active Zones During Synapse Development References 3 Basics of Cellular Neurophysiology Neurons are Excitable Cells Ions in and Around Neurons Membrane Potential and Capacitance Movement of Ions Across the Cell Membrane Calculating the Equilibrium Potential for an Ion Multiple Ions Contribute to the Resting Membrane Potential Calculating the Membrane Potential Ion Fluxes at Resting Membrane Potentials Driving Force on an Ion Maintaining Ionic Concentrations Membrane Conductance and Resistance Ohm’s Law References 4 Ion Channels and Action Potential Generation Ion Channels Gating of Ion Channels Voltage-Gated Ion Channels S4 Segments Act as Voltage Sensors Voltage-Gated Ion Channel Structure Ion Channel Permeation and Selectivity Ion Channel Auxiliary Proteins Ionic Currents Through Voltage-Gated Ion Channels Voltage-Dependent Activation Current–Voltage Relationships Action Potentials Inactivation and Deactivation of Voltage-Gated Ion Channels Mechanisms of Channel Inactivation Action Potential Refractory Periods The distributions of sodium and potassium ions across the cell membrane do not change significantly during a single action ... Action Potential Propagation Myelin and Nodes of Ranvier References 5 Electrical Synapses History of Electrical Synapses Early Evidence in Favor of Electrical Communication in the Nervous System Discovery of Electrical Synapses Structure and Physiological Characteristics of Electrical Syapses Gap Junction Structure Physiological Characteristics of Electrical Synapses Roles of Electrical Synapses The Role of Electrical Synapses in the Developing Mammalian Nervous System Electrical Synapses in the Development of the Neuromuscular Synapse Electrical Synapses in the Development of Cortical Synapses Roles of Electrical Synapses in the Adult Mammalian Nervous System Electrical Synapse Plasticity References Part II: Regulation of Chemical Transmitter Release 6 Function of Chemical Synapses and the Quantal Theory of Transmitter Release Costs and Advantages of Chemical Communication Electrical Footprints of Chemical Transmitter Release Spontaneous Release of Single Neurotransmitter Vesicles The Quantal Theory of Chemical Transmitter Release Quantal Analysis of Chemical Transmitter Release at the Neuromuscular Junction Quantal Analysis of Chemical Transmitter Release at Central Synapses Optical Quantal Analysis Summary References 7 Calcium Homeostasis, Calcium Channels, and Transmitter Release Calcium as a Trigger for Neurotransmitter Release The Distribution of Calcium Ions Across the Cell Membrane Cellular Mechanisms Used to Maintain the Very Low Intracellular Calcium Concentration Presynaptic Calcium Ion Plasma Membrane Transporters Presynaptic Cellular Organelles That Buffer Calcium Nerve Terminals Contain Endogenous Calcium Buffer Proteins Control of Neurotransmitter Release by Calcium Ions The Nonlinear Relationship Between Calcium and Neurotransmitter Release Where Are Calcium Channels Located Within the Nerve Terminal? Cytoplasmic Calcium Microdomains Voltage-Gated Calcium Channels in Nerve Terminals The Structure of Voltage-Gated Calcium Channels Calcium Entry Into a Presynaptic Terminal During an Action Potential The Role of Potassium Channels in Shaping Calcium Entry During an Action Potential References 8 Cellular and Molecular Mechanisms of Exocytosis Discovery of the Mechanisms of Neurotransmitter Release Is Neurotransmitter Released Through a Channel in the Presynaptic Membrane? Experimental Evidence Supporting Synaptic Vesicle Fusion With Plasma Membrane as the Mechanism for Quantal Transmitter Release Biochemical Mechanims of Calcium-Triggered Synaptic Vesicle Fusion Study of Vesicle Fusion Proteins Involved in Calcium-Triggered Vesicle Release Experimental Evidence That the CORE Complex Is Critical for Transmitter Release How Do Synaptic Vesicles Move to the Correct Location in the Nerve Terminal Prior to Release? How Are SNARE Proteins Directed to Coil Together Properly to “Dock” a Synaptic Vesicle to the Plasma Membrane? Coupling of Voltage-Gated Calcium Channels to the Active Zone How Do SNARE Proteins of the CORE Complex Work With Synaptotagmin (the Calcium Sensor) to Regulate Calcium-Triggered Transm... Evidence That Synaptotagmin Is the Calcium Sensor at Active Zones Recovery and Disassembly of the SNARE Protein CORE Complex After Synaptic Vesicle Fusion References 9 Cellular and Molecular Mechanisms of Endocytosis and Synaptic Vesicle Trafficking Retrieval and Reuse of Synaptic VESICLE Membrane Endocytosis Occurs Outside the Active Zone Mechanisms of Endocytosis Clathrin-Mediated Endocytosis Bulk Endocytosis Kiss-and-Run Synaptic Vesicle Pools Synaptic Vesicle Trafficking in the Nerve Terminal References Part III: Receptors and Signaling 10 Introduction to Receptors Neurotransmitter Receptors Can Be Divided Into Two General Classes: Ionotropic and Metabotropic GTP-Binding Protein (G-Protein)-Coupled Receptors Enzyme-Linked Receptors Cytoplasmic Receptors Comparison Between Ionotropic and Metabotropic Receptors References 11 Ionotropic Receptors The Pentameric Ligand-Gated Ion Channel Family (Cys-Loop Receptors) Nicotinic Acetylcholine Receptors The 5-HT3 Serotonin Receptor GABAA Receptors Glycine Receptors Zinc-Activated Channel Receptors The Glutamate Ionotropic Receptor Family NMDA Receptors AMPA and Kainate Glutamate Receptors The Trimeric Receptor Family P2X Receptors for ATP Acid-Sensing Ion Channels The Transient Receptor Potential Channel Family References 12 Metabotropic G-Protein-Coupled Receptors and Their Cytoplasmic Signaling Pathways Common Themes in Receptor Coupling to Heterotrimeric G-Proteins Families of Heterotrimeric G-Proteins How Is Metabotropic Signaling Terminated? The Four Most Common G-Protein-coupled Signaling Pathways in the Nervous System Direct Ion Channel Pathway cAMP Pathway Phosphoinositol Pathway Arachidonic Acid Pathway Other G-Protein-Coupled Signaling Pathways in the Nervous System Phosphoinositide 3 Kinase (PI3K) Pathway MAP Kinase and Rho Pathways The Src Pathway Specificity of Coupling Between Receptors and G-Protein-Coupled Signaling Cascades Mechanisms That Prevent Unintended Crosstalk Between Receptor-Mediated Signaling Systems References 13 Synaptic Integration Within Postsynaptic Neurons Passive Membrane Properties Spines Are Specialized Postsynaptic Compartments on Dendrites Active Membrane Properties References 14 Synaptic Plasticity Short-Term Synaptic Plasticity Mechanisms of Residual Calcium Effects on Transmitter Release Metabotropic Receptor-Mediated Plasticity of Ionotropic Signaling Habituation and Sensitization Long-Term Synaptic Plasticity Clinical Cases That Focused the Investigation of Long-Term Synaptic Plasticity Long-Term Potentiation Physiological Stimulus Patterns That Can Induce Long-Term Potentiation Associative Long-Term Potentiation Spike Timing-Dependent Plasticity Long-Term Depression Heterosynaptic Plasticity Synaptic Signaling Mechanisms of Long-Term Potentiation and Long-Term Depression Metaplasticity Plasticity Modulation Homeostatic Synaptic Plasticity References Part IV: Chemical Transmitters 15 Introduction to Chemical Transmitter Systems Neurotransmitter Versus Neuromodulator Criteria Used to Classify a Signaling Molecule as a Neurotransmitter Neurotransmitter Characteristics Synthetic Pathways Regulation of Neurotransmitter Synthesis Methods for Termination of Neurotransmitter Action Types of Neurotransmitters Type 1: “Classical” Neurotransmitters (ACh, GABA, Monoamines) Type 2: Amino Acid Neurotransmitters (Glutamate, Glycine) Type 3: Gaseous Messengers: Nitric Oxide, Carbon Monoxide, and Hydrogen Sulfide Type 4: Neuropeptides References 16 Acetylcholine History of the Discovery of Acetylcholine and Its Identity as a Neurotransmitter Synthesis, Release, and Termination of Action of Acetylcholine Acetylcholine Synthesis Packaging of Acetylcholine Into Synaptic Vesicles Release of Acetylcholine Regulation of Acetylcholine Synthesis Termination of Action for Acetylcholine Roles of Acetylcholine in the Nervous System Acetylcholine in the Peripheral Nervous System Acetylcholine in the Central Nervous System Sources of Acetylcholine in the Central Nervous System Cholinergic Synaptic Transmission in the Autonomic Nervous System Drugs and Other Compounds that Affect Cholinergic Signaling Parasympathomimetic Drugs Anticholinergic Drugs Compounds That Inhibit Acetylcholinesterase References 17 Monoamine Transmitters Catecholamine Neurotransmitters Catecholamine Synthesis Step 1: Tyrosine to l-Dihydroxyphenylalanine Step 2: l-Dihydroxyphenylalanine to Dopamine Step 3: Dopamine to Norepinephrine Step 4: Norepinephrine to Epinephrine Regulation of Catecholamine Synthesis Termination of Action of Catecholamines Serotonin Serotonin Synthesis Regulation of Serotonin Synthesis Termination of Action of Serotonin Histamine Histamine Synthesis Regulation of Histamine Synthesis Termination of Action of Histamine Projections of Monoaminergic Neurons and Functions of Monoamines in the Nervous System Dopamine Norepinephrine Epinephrine Serotonin Sources of Histamine and Its Roles in Brain Function Therapeutic Drugs Related to Monoamine Neurotransmitters Therapeutic Drugs That Stimulate Monoaminergic Receptors Therapeutic Drugs That Block Monoaminergic Receptors Therapeutic Drugs That Affect VMAT2 Therapeutic Drugs That Inhibit Monoamine Oxidase Therapeutic Drugs That Inhibit the Reuptake of Monoamines Monoaminergic Drugs of Abuse References 18 Amino Acid Neurotransmitters Glutamate Glutamate Synthesis Packaging of Glutamate Into Vesicles Identity of Action for Glutamate Regulation of Glutamate Synthesis Termination of Glutamate Action GABA GABA Synthesis Termination of GABA Action GABA and the Neurological Disease Schizophrenia Glycine Glycine Synthesis Termination of Glycine Action Functions of Glycinergic Neurons References 19 Neuropeptide Transmitters How Do Neuropeptides Differ From Classical (Type 1) Neurotransmitters? Neuropeptide Synthesis, Release, and Regulation Neuropeptide Synthesis Vesicular Release of Neuropeptides Regulation of Neuropeptide Synthesis Neuropeptide Receptors and Their Effects on Neurotransmitter Release Neuropeptide Y as a Model for Neuropeptide Action Effects of Neuropeptide Y on Behavior Roles of Neuropeptide Y in Feeding Behavior Role of Neuropeptide Y in Seizures References 20 Gaseous Neurotransmitters Nitric Oxide Synthesis of Nitric Oxide Regulation of Nitric Oxide Synthesis How Does Nitric Oxide Act as a Neurotransmitter, and What Roles Does It Play in the Nervous System? Termination of Action of Nitric Oxide Nitric Oxide Control of Autonomic Function Effects of Nitric Oxide in the Central Nervous System Carbon Monoxide Regulation of Carbon Monoxide Synthesis Hydrogen Sulfide Synthesis and Regulation of Hydrogen Sulfide Roles of Hydrogen Sulfide in the Brain References 21 The Use of Multiple Neurotransmitters at Synapses Overview and Historical Perspective Functional Implications of Multiple Neurotransmitter Release Cotransmission and Corelease of Neurotransmitters Peptidergic Cotransmission Segregation of Small-Molecule Neurotransmitters Into Separate Vesicle Pools Spatial Segregation of Neurotransmitters Neurotransmitter Corelease Vesicular Synergy as a Function of Neurotransmitter Corelease Purinergic Cotransmission Neurotransmitter Specification and Switching The Neurotransmitter Phenotype of a Synapse can Change During Development Neurotransmitter–Receptor Matching Neurotransmitter Switching in the Developing Nervous System Developmental Neurotransmitter Switching: The Noradrenergic-to-Cholinergic Switch in Sympathetic Neurons Spontaneous Electrical Activity Drives Neurotransmitter Switching in Nervous System Development Transient Glutamate Expression in Synaptic Refinement During Development Sensation-Mediated Neurotransmitter Switching Neurotransmitter Switching in the Adult Nervous System “Stimulus-mediated” Neurotransmitter Switching in Mature Neurons Neurotransmitter Switching as a Compensatory Mechanism in Disease Summary References 22 Complex Signaling Within Tripartite Synapses The Role of Astrocytes in Synaptic Function Uptake of Neurotransmitters by Astrocytic Transporters Astrocytes Maintain Potassium in Extracellular Fluid Ion Channels in Astrocytes Interactions Between Astrocytes: Gap Junctions and Calcium Waves Release of Neurotransmitters From Astrocytes Do Astrocytes Play a Role in Information Processing Within the Brain? References Glossary Index Back Cover