Synaptic Transmission

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
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