From Neuron to Brain

by Nicholls, John G.; Martin, A. Robert; Wallace, Bruce G.; Fuchs, Paul A.

• ISBN13: 9780878934393
• ISBN10: 0878934391
• Edition: 4th
• Format: Hardcover
• Copyright: 2001-01-01
• Publisher: Sinauer Associates Inc

Summary

International School for Advanced Studies, Trieste, Italy. A textbook for readers with an interest in the human nervous system with little or no background in the biological sciences. Describes how nerve cells transmit signals, how the signals are put together, and how they coordinate, leading to higher functions. Previous edition: c1992. Illustrated in color.

Table of Contents

PART 1 Introduction
Principles of Signaling and Organization	3	(22)
Signaling in Simple Neuronal Circuits	4	(1)
Complex Neuronal Circuitry in Relation to Higher Functions	4	(1)
Organization of the Retina	5	(4)
Shapes and Connections of Neurons	5	(2)
Cell Body, Dendrites, and Axons	7	(1)
Techniques for Identifying Neurons and Tracing Their Connections	8	(1)
Nonneuronal Cells	8	(1)
Grouping of Cells According to Function	8	(1)
Subtypes of Cells in Relation to Function	9	(1)
Convergence and Divergence of Connections	9	(1)
Signaling in Nerve Cells	9	(10)
Classes of Electrical Signals	10	(1)
Universality of Electrical Signals	10	(1)
Techniques for Recording Signals from Neurons with Electrodes	11	(1)
Noninvasive Techniques for Recording Neuronal Activity	11	(1)
Spread of Local Graded Potentials and Passive Electrical Properties of Neurons	12	(2)
Spread of Potential Changes in Bipolar Cells and Photo-receptors	14	(1)
Properties of Action Potentials	14	(1)
Propagation of Action Potentials along Nerve Fibers	15	(1)
Action Potentials as the Neural Code	15	(1)
Synapses: The Sites for Cell-to-Cell Communication	15	(1)
Chemically Mediated Synaptic Transmission	15	(1)
Excitation and Inhibition	16	(1)
Electrical Transmission	16	(1)
Modulation of Synaptic Efficacy	17	(1)
Integrative Mechanisms	18	(1)
Complexity of the Information Conveyed by Action Potentials	19	(1)
Cellular and Molecular Biology of Neurons	19	(1)
Signals for Development of the Nervous System	20	(1)
Regeneration of the Nervous System after Injury	21	(4)
PART 2 Signaling in the Nervous System
Ion Channels and Signaling	25	(14)
Properties of Ion Channels	26	(3)
The Nerve Cell Membrane	26	(1)
What Does an Ion Channel Look Like?	27	(1)
Channel Selectivity	27	(1)
Open and Closed States	27	(1)
Modes of Activation	28	(1)
Measurement of Single-Channel Currents	29	(8)
Patch Clamp Recording	29	(1)
Recording Configurations with Patch Electrodes	29	(2)
Intracellular Recording with Microelectrodes	31	(1)
Intracellular Recording of Channel Noise	31	(2)
Channel Conductance	33	(1)
Conductance and Permeability	34	(1)
Equilibrium Potential	34	(1)
The Nernst Equation	35	(1)
Driving Force	36	(1)
Nonlinear Current-Voltage Relations	36	(1)
Ion Permeation through Channels	36	(1)
Significance of Ion Channels	37	(1)
Box 2.1 Measuring Channel Conductance	37	(2)
Structure of Ion Channels	39	(22)
The Nicotinic Acetylcholine Receptor	41	(8)
Physical Properties of the ACh Receptor	42	(1)
Amino Acid Sequence of AChR Subunits	43	(1)
Higher-Order Chemical Structure	44	(1)
Channel Structure and Function	44	(2)
Fetal and Adult ACh Receptors in Mammalian Muscle	46	(1)
Which AChR Subunits Line the Pore?	47	(1)
High-Resolution Imaging of the ACh Receptor	47	(1)
Open and Closed States of the ACh Receptor	48	(1)
Diversity of Neuronal AChR Subunits	49	(1)
Subunit Composition of Neuronal ACh Receptors	49	(1)
A Receptor Superfamily	49	(1)
GABA, Glycine, and 5-HT Receptors	49	(1)
Ion Selectivity of Ligand-Gated Channels	50	(1)
Voltage-Activated Channels	50	(5)
The Voltage-Activated Sodium Channel	51	(1)
Amino Acid Sequence and Tertiary Structure of the Sodium Channel	51	(1)
Voltage-Activated Calcium Channels	51	(1)
Voltage-Activated Potassium Channels	52	(1)
How Many Subunits Make a Potassium Channel?	53	(1)
Pore Formation in Voltage-Activated Channels	54	(1)
High-Resolution Imaging of a Potassium Channel	54	(1)
Other Channels	55	(3)
Voltage-Activated Chloride Channels	55	(1)
Inward-Rectifying Potassium Channels	56	(1)
ATP-Activated Channels	56	(1)
Glutamate Receptors	56	(1)
Channels Activated by Cyclic Nucleotides	57	(1)
Diversity of Subunits	58	(1)
Conclusion	58
Cloning Receptors and Channels	40	(5)
Classification of Amino Acids	45	(1)
Expression of Receptors and Channels in Xenopus Oocytes	46	(15)
Transport Across Cell Membranes	61	(16)
The Sodium-Potassium Exchange Pump	62	(2)
Biochemical Properties of Sodium-Potassium ATPase	62	(1)
Experimental Evidence that the Pump Is Electrogenic	63	(1)
Mechanism of Ion Translocation	63	(1)
Calcium Pumps	64	(2)
Sarcoplasmic and Endoplasmic Reticulum Calcium ATPases	66	(1)
Plasma Membrane Calcium ATPase	66	(1)
Sodium-Calcium Exchange	66	(3)
The NCX Transport System	67	(1)
Reversal of Na-Ca Exchange	67	(2)
Sodium-Calcium Exchange in Retinal Rods	69	(1)
Chloride Transport	69	(1)
Chloride-Bicarbonate Exchange	69	(1)
Potassium-Chloride Cotransport	70	(1)
Inward Chloride Transport	70	(1)
Transport of Neurotransmitters	70	(2)
Transport into Presynaptic Vesicles	70	(1)
Transmitter Uptake	71	(1)
Molecular Structure of Transporters	72	(2)
ATPases	72	(1)
Sodium-Calcium Exchangers	72	(1)
Other Ion Transporters	73	(1)
Transport Molecules for Neurotransmitters	74	(1)
Significance of Transport Mechanisms	74	(3)
Ionic Basis of the Resting Potential	77	(14)
A Model Cell	78	(3)
Ionic Equilibrium	78	(1)
Electrical Neutrality	79	(1)
The Effect of Extracellular Potassium and Chloride on Membrane Potential	80	(1)
Membrane Potentials in Squid Axons	81	(7)
The Effect of Sodium Permeability	83	(1)
The Constant Field Equation	84	(1)
The Resting Membrane Potential	85	(1)
Chloride Distribution	86	(1)
An Electrical Model of the Membrane	86	(1)
Predicted Values of Membrane Potential	87	(1)
Contribution of the Sodium-Potassium Pump to the Membrane Potential	87	(1)
Ion Channels Associated with the Resting Potential	88	(1)
Changes in Membrane Potential	88	(3)
Ionic Basis of the Action Potential	91	(22)
Sodium and Potassium Currents	92	(2)
How Many Ions Enter and Leave during an Action Potential?	93	(1)
Positive and Negative Feedback during Conductance Changes	93	(1)
Measuring Conductance	93	(1)
Voltage Clamp Experiments	94	(9)
Capacitative and Leak Currents	94	(1)
Currents Carried by Sodium and Potassium	95	(1)
Selective Poisons for Sodium and Potassium Channels	96	(1)
Dependence of Ion Currents on Membrane Potential	97	(1)
Inactivation of the Sodium Current	98	(2)
Sodium and Potassium Conductances as Functions of Potential	100	(1)
Quantitative Description of Sodium and Potassium Conductances	101	(1)
Reconstruction of the Action Potential	101	(1)
Threshold and Refractory Period	102	(1)
Gating Currents	103	(7)
Activation and Inactivation of Single Channels	104	(1)
Molecular Mechanisms of Activation and Inactivation	105	(1)
Gating of Voltage-Activated Channels	105	(1)
Sodium Channel Inactivation	106	(1)
Inactivation of Potassium A-Channels	107	(1)
Kinetic Models of Channel Activation and Inactivation	108	(1)
Properties of Channels Associated with the Action Potential	109	(1)
Other Potassium Channels Contributing to Repolarization	109	(1)
The Role of Calcium in Excitation	110
Calcium Action Potentials	110	(1)
Calcium Ions and Excitability	110
The Voltage Clamp	95	(18)
Neurons as Conductors of Electricity	113	(20)
Passive Electrical Properties of Nerve and Muscle Membranes	114	(7)
Nerve and Muscle Fibers as Cables	114	(1)
Flow of Current in a Cables	115	(1)
Input Resistance and Length Constant	116	(1)
Membrane Resistance and Longitudinal Resistance	116	(1)
Calculating Membrane Resistance and Internal Resistance	117	(1)
Specific Resistance	117	(1)
The Effect of Diameter on Cable Characteristics	118	(1)
Membrane Capacitance	118	(2)
Time Constant	120	(1)
Capacitance in a Cable	121	(1)
Propagation of Action Potentials	121	(7)
Conduction Velocity	122	(1)
Myelinated Nerves and Saltatory Conduction	123	(1)
Conduction Velocity in Myelinated Fibers	123	(2)
Distribution of Channels in Myelinated Fibers	125	(1)
Channels in Demyelinated Axons	125	(1)
Geometry and Conduction Block	126	(2)
Conduction in Dendrites	128	(1)
Pathways for Current Flow between Cells	128
Structural Basis for Electrical Coupling: The Gap Junction	129
Electrotonic Potentials and the Membrane Time Constant	120	(5)
Classification of Nerve Fibers in Vertebrates	125	(2)
Stimulating and Recording with External Electrodes	127	(3)
Current Flow Between Cells	130	(3)
Properties and Functions of Neuroglial Cells	133	(22)
Historical Perspective	134	(1)
Appearance and Classification of Glial Cells	134	(2)
Structural Relations between Neurons and Glia	136	(1)
Physiological Properties of Neuroglial Cell Membranes	137	(3)
Ion Channels, Pumps, and Receptors in Glial Membranes	138	(2)
Electrical Coupling between Glial Cells	140	(1)
Functions of Neuroglial Cells	140	(6)
Myelin and the Role of Neuroglial Cells in Axonal Conduction	140	(2)
Glial Cells, CNS Development, and Secretion of Growth Factors	142	(2)
Role of Microglial Cells in CNS Repair and Regeneration	144	(1)
Schwann Cells as Pathways for Outgrowth in Peripheral Nerves	145	(1)
A Cautionary Note	146	(1)
Effects of Neuronal Activity on Glial Cells	146	(4)
Potassium Accumulation in Extracellular Space	146	(1)
Current Flow and Potassium Movement through Glial Cells	147	(1)
Spatial Buffering of Extracellular Potassium Concentration by Glia	147	(1)
Effects of Transmitters on Glial Cells	148	(1)
Release of Transmitters by Glial Cells	149	(1)
Calcium Waves in Glial Cells	149	(1)
Transfer of Metabolites from Glial Cells to Neurons	150	(1)
Immediate Effects of Glial Cells on Neuronal Signaling	150	(1)
Glial Cells and the Blood-Brain Barrier	150	(3)
Astrocytes and Blood Flow through the Brain: A Speculation	153	(1)
Glial Cells and Immune Responses of the CNS	153
The Blos-Brain Barrier	151	(4)
Principles of Direct Synaptic Transmission	155	(22)
Nerve Cells and Synaptic Connections	156	(2)
Chemical Synaptic Transmission in the Autonomic Nervous System	157	(1)
Chemical Synaptic Transmission at the Vertebrate Skeletal Neuromuscular Junction	157	(1)
Electrical Synaptic Transmission	158	(2)
Identification and Characterization of Electrical Synapses	158	(1)
Synaptic Delay at Chemical and Electrical Synapses	159	(1)
Chemical Synaptic Transmission	160	(9)
Synaptic Structure	160	(2)
Synaptic Potentials at the Neuromuscular Junction	162	(1)
Mapping the Region of the Muscle Fiber Receptive to ACh	163	(1)
Other Techniques for Determining the Distribution of ACh Receptors	164	(2)
Measurement of Ionic Currents Produced by ACh	166	(1)
Significance of the Reversal Potential	167	(1)
Relative Contributions of Sodium, Potassium, and Calcium to the End Plate Potential	167	(1)
Resting Membrane Conductance and Synaptic Potential Amplitude	168	(1)
Electrical Model of the Motor End Plate	169	(2)
Kinetics of Currents through Single ACh Receptor Channels	169	(2)
Direct Synaptic Inhibition	171	(6)
Reversal of Inhibitory Potentials	171	(2)
Presynaptic Inhibition	173	(1)
Desensitization	174	(1)
Receptors Mediating Direct and Indirect Chemical Transmission	175	(2)
Indirect Mechanisms of Synaptic Transmission	177	(22)
Metabotropic receptors and G Proteins	178	(2)
Structure of Metabotropic Receptors	178	(1)
G Protein Structure and Function	179	(1)
Desensitization	180	(1)
Direct Modulation of Channel Function by G proteins	180	(4)
G Protein Activation of Potassium Channels	181	(1)
G Protein Inhibition of Calcium Channels	182	(2)
G Protein Activation of Cytoplasmic Second Messenge Systems	184	(9)
β-Adrenergic Receptors Activate Calcium Channels via a G Protein-Adenylyl Cyclase Pathway	184	(2)
Regulation of Calcium Channel Activity by Other Signaling pathways	186	(1)
Modulation of Calcium Channel Activity by Phosphorylation	186	(2)
G Protein Activation of Phospholipase C	188	(1)
G Protein Activation of Phospholipase A	188	(1)
Signaling via Nitric Oxide and Carbon Monoxide	189	(4)
Modulation of Potassium and Calcium Channels by Indirectly Coupled Receptors	193	(1)
Calcium as an Intracellular Second Messenger	193	(2)
Calcium-Mediated Rapid Synaptic Inhibition	193	(1)
Complexity of Calcium Signaling Pathways	194	(1)
Prolonged Time Course of Indirect Transmitter Action	195
Identifying Responses Mediated by G Proteins	181	(6)
Cyclic AMP as a Second Messenger	187	(3)
Diacylglycerol and IP3 as Second Messengers	190	(2)
Formation and Metabolism of Arachidonic Acid	192	(7)
Transmitter Release	199	(28)
Characteristics of Transmitter Release	200	(6)
Axon Terminal Depolarization and Release	200	(1)
Synaptic Delay	200	(1)
Evidence that Calcium Is Required for Release	201	(1)
Measurement of Calcium Entry into Presynaptic Nerve Terminals	202	(2)
Localization of Calcium Entry Sites	204	(1)
Role of Depolarization in Release	204	(2)
Quantal Release	206	(7)
Spontaneous Release of Multimolecular Quanta	206	(1)
Nonqunatal Release	207	(1)
Fluctuations in the End-Plate Potential	208	(1)
Statistical Analysis of the End-Plate Potential	209	(2)
Quantum Content at Neuronal Synapses	211	(1)
Number of Molecules in a Quantum	211	(1)
Number of Channels Activated by a Quantum	211	(2)
Changes in Mean Quantal Size at the Neuromuscular Junction	213	(1)
Vesicle Hypothesis of Transmitter Release	213	(14)
Ultrastructure of Nerve Terminals	214	(2)
Release of Vesicle Contents by Exocytosis	216	(1)
Morphological Evidence for Exocytosis	217	(2)
Recycling of Vesicle Components	219	(1)
Monitoring Exocytosis and Endocytosis in Living Cells	220	(7)
Synaptic Plasticity	227	(16)
Short-Term Changes in Signaling	229	(3)
Facilitation and Depression of Transmitter Release	229	(1)
Role of Calcium in Facilitation	230	(1)
Augmentation of Synaptic Transmission	230	(1)
Posttetanic Potentiation	231	(1)
Long-Term Changes in Signaling	232	(11)
Long-Term Potentiation	232	(1)
Associative LTP in Hippocampal Pyramidal Cells	233	(2)
Mechanisms Underlying the Induction of LTP	235	(1)
LTP Expression	235	(1)
Silent Synapses	236	(1)
Up-Regulation of Receptors	236	(2)
Presynaptic LTP	238	(1)
Long-Term Depression	238	(1)
LTD in the Cerebellum	239	(1)
Induction of LTD	240	(1)
Second Messenger Systems Mediating LTD	240	(1)
LTD Expression	241	(1)
Significance of Changes in Synaptic Efficacy	241	(2)
Cellular and Molecular Biochemistry of Synaptic Transmission	243	(28)
Neurotransmitters	244	(3)
The Identification of Transmitters	244	(1)
Neurotransmitters as Messengers	245	(1)
Transmitter Molecules	245	(2)
Neurotransmitter Synthesis	247	(7)
Synthesis of ACh	248	(2)
Synthesis of Dopamine and Norepinephrine	250	(1)
Synthesis of 5-HT	251	(1)
Synthesis of GABA	252	(1)
Synthesis of Glutamate	253	(1)
Short- and Long-Term Regulation of Transmitter Synthesis	253	(1)
Synthesis of Neuropeptides	254	(1)
Storage of Transmitters in Synaptic Vesicles	254	(2)
Axonal Transport	256	(2)
Rate and Direction of Axonal Transport	256	(2)
Microtubules and Fast Transport	258	(1)
Mechanism of Slow Axonal Transport	258	(1)
Transmitter Release and Vesicle Recycling	258	(6)
Sorting of Vesicles within the Nerve Terminal	258	(3)
Conserved Mechanisms for Vesicle Trafficking	261	(1)
Synaptotagmin and the Calcium Dependence of Neurotransmitter Release	261	(1)
Bacterial Neurotoxins Target the SNARE Complex	261	(2)
Recovery of Synaptic Vesicle Membrane Components by Endocytosis	263	(1)
Transmitter Receptor Localization	264	(1)
Presynaptic Receptors	265	(1)
Removal of Transmitters from the Synaptic Cleft	265
Removal of ACh by Acetylcholinesterase	265	(2)
Removal of ATP by Hydrolysis	267	(1)
Removal of Transmitters by Uptake	267
The SNARE Hypothesis	262	(9)
Neurotransmitters in the Central Nervous System	271	(20)
Mapping Transmitter Distribution	273	(7)
GABA and Glycine: Inhibitory Transmitters in the CNS	274	(1)
GABA Receptors	275	(1)
Modulation of GABAA Receptor Function by Benzodiazepines and Barbiturates	276	(1)
Glutamate Receptors in the CNS	277	(1)
Nitric Oxide as a Transmitter in the CNS	277	(1)
Acetylcholine: Basal Forebrain Nuclei	278	(1)
Cholinergic Neurons, Cognition, and Alzheimer's Disease	278	(2)
ATP and Adenosine as CNS Transmitters	280	(1)
Peptide Transmitters in the CNS	280	(2)
Substance P	280	(1)
Opioid Peptides	281	(1)
Regulation of Central Nervous System Function by Biogenic Amines	282
Norepinephrine: The Locus Coeruleus	282	(1)
5-HT: The Raphe Nuclei	283	(1)
Histamine: The Tuberomammillary Nucleus	284	(1)
Dopamine: The Substantia Nigra	284	(2)
Targeting Specific Synapses	286
Molecular Methods and CNS Transmitters	272	(19)
PART 3 Integrative Mechanisms
Cellular Mechanisms of Integration and Behavior in Leeches, Ants, and Bees	291	(24)
From Neurons to Behavior and Vice Versa	292	(12)
Integration by Individual Neurons in the CNS of the Leech	293	(1)
Leech Ganglia: Semiautonomous Units	293	(1)
Sensory Cells in Leech Ganglia	293	(3)
Motor Cells	296	(1)
Connections of Sensory and Motor Cells	297	(2)
Short-Term Changes in Synaptic Efficacy	299	(1)
Membrane Potential, Presynaptic Inhibition, and Transmitter Release	299	(2)
Repetitive Firing and Conduction Block	301	(1)
Higher Levels of Integration	302	(1)
The S Interneuron and Sensitization	303	(1)
Navigation by Ants and Bees	304	(9)
The Desert Ant's Pathway Home	304	(3)
The Use of Polarized Light as a Compass	307	(1)
Polarized Light Detection by the Ant's Eye	308	(1)
Strategies for Finding the Nest	309	(1)
Neural Mechanisms for Navigation	310	(1)
Polarized Light and Twisted Photoreceptors in Bees	311	(1)
Use of Magnetic Fields by Bees for Navigation	312	(1)
Why Should One Work on Invertebrate Nervous Systems?	313	(2)
Autonomic Nervous System	315	(18)
Functions under Involuntary Control	316	(5)
Sympathetic and Parasympathetic Nervous Systems	316	(2)
Synaptic Transmission in Autonomic Ganglia	318	(2)
M-Currents in Autonomic Ganglia	320	(1)
Synaptic Transmission by Postganglionic Axons	321	(2)
Purinergic Transmission	322	(1)
Sensory Inputs to the Autonomic Nervous System	323	(1)
The Enteric Nervous System	324	(1)
Regulation of Autonomic Functions by the Hypothalamus	324	(3)
Hypothalamic Neurons that Release Hormones	327	(1)
Distribution and Numbers of GnRH Cells	327	(1)
Circadian Rhythms	328
The Path to Understanding Sympathetic Mechanisms	323	(10)
Transduction of Mechanical and Chemical Stimuli	333	(22)
Stimulus Coding by Mechanoreceptors	334	(6)
Short and Long Receptors	334	(1)
Encoding Stimulus Parameters by Stretch Receptors	335	(1)
The Crayfish Stretch Receptor	336	(1)
Muscle Spindles	336	(2)
Responses to Static and Dynamic Muscle Stretch	338	(1)
Mechanisms of Adaptation in Mechanoreceptors	339	(1)
Adaptation in the Pacinian Corpuscle	339	(1)
Transduction of Mechanical Stimuli	340	(7)
Mechanosensory Hair Cells of the Verebrate Ear	340	(1)
Structure of Hair Cell Receptors	341	(2)
Transduction by Hair Bundle Deflection	343	(1)
Tip Links and Gating Springs	344	(1)
Transduction Channels in Hair Cells	345	(1)
Adaptation of Hair Cells	345	(2)
Olfaction	347	(3)
Olfactory Receptors	347	(1)
Cyclic Nucleotide-Gated Channels in Olfactory Receptors	348	(1)
Coupling the Receptor to Ion Channels	349	(1)
Odorant Specificity	349	(1)
Mechanisms of Taste (Gustation)	350	(2)
Taste Receptor Cells	350	(1)
Salt Taste and Sour Taste	351	(1)
Sweet Taste and Bitter Taste	351	(1)
Molecular Receptors for Glutamate and Chili	352	(1)
Transduction of Nociceptive and Thermal Stimuli	352
Activation and Sensitization of Nociceptors	352
Sensory Epithelia of the Inner Ear	342	(13)
Processing of Somato-Sensory and Auditory Signals	355	(24)
The Somatosensory System: Tactile Recognition	356	(10)
Organization of Receptors for Fine Touch	356	(1)
Stimulus Coding	357	(1)
Central Pathways	358	(1)
The Somatosensory Cortex	358	(1)
Response Properties of Cortical Neurons	359	(1)
Surround Inhibition	360	(1)
Parallel Processing of Sensory Modalities	361	(1)
Secondary and Associated Somatosensory Cortices	362	(1)
Pain and Temperature Pathways	363	(1)
Central Pathways for Pain	364	(2)
The Auditory System: Encoding Sound Frequency	366
The Cochlea	366	(1)
Frequency Selectivity: Mechanical Tuning	367	(1)
Efferent Inhibition of the Cochlea	368	(2)
Electromotility of Mammalian Cochlear Hair Cells	370	(1)
Electrical Tuning of Hair Cells	370	(2)
Hair Cell Potassium Channels and Tuning	372	(1)
The Auditory Pathway	372	(2)
Auditory Cortex	374	(1)
Sound Localization	375
Brodmann's Areas	364	(15)
Transduction and Signaling in the Retina	379	(28)
The Eye	380	(1)
Anatomical Pathways in the Visual System	380	(1)
Convergence and Divergence of Connections	381	(1)
The Retina	381	(3)
Layering of Cells in the Retina	381	(1)
Rods and Cones	382	(1)
Arrangement and Morphology of Photoreceptors	382	(1)
Electrical Responses of Vertebrate Photoreceptors to Light	383	(1)
Visual Pigments	384	(3)
Absorption of Light by Visual Pigments	384	(1)
Structure of Rhodopsin	385	(1)
Cones and Color Vision	385	(2)
Color Blindness	387	(1)
Transduction by Photoreceptors	387	(7)
Properties of the Photoreceptor Channels	388	(1)
Molecular Structure of Cyclic GMP-gated Channels	389	(1)
The Cyclic GMP Cascade	390	(1)
Vertebrate Photoreceptors with Depolarizing Responses to Light	390	(2)
Amplification through the Cyclic GMP Cascade	392	(1)
Responses to Single Quanta of Light	392	(2)
Transmission from Photoreceptors to Bipolar Cells	394	(5)
Bipolar, Horizontal, and Amacrine Cells	394	(1)
Transmitters in the Retina	395	(1)
The Concept of Receptive Fields	396	(1)
Responses of Bipolar Cells	396	(1)
Receptive Field Organization of Bipolar Cells	397	(1)
Horizontal Cells and Surround Inhibition	398	(1)
Significance of Receptive Field Organization of Bipolar Cells	398	(1)
Receptive Fields of Ganglion Cells	399
The Output of the Retina	399	(1)
The Use of Discrete Visual Stimuli in Intact Animals for Defining Receptive Fields	400	(1)
Ganglion Cell Receptive Field Organization	400	(1)
Sizes of Receptive Fields	400	(2)
Classification of Ganglion Cells	402	(1)
Synaptic Inputs to Ganglion Cells Responsible for Receptive Field Organization	402	(1)
What Information Do Ganglion Cells Convey?	402
Adaptation of Photoreceptors	391	(16)
Signaling in the Lateral Geniculate Nucleus and the Primary Visual Cortex	407	(20)
The Lateral Geniculate Nucleus	408	(3)
Visual Field Maps in the Lateral Geniculate Nucleus	409	(1)
Functional Layers of the Lateral Geniculate Nucleus	410	(1)
Cytoarchitecture of the Cortex	411	(3)
Inputs, Outputs, and Layering of Cortex	413	(1)
Segregation of Geniculate Inputs in Layer 4	414	(1)
Strategies for Exploring the Cortex	414	(13)
Cortical Receptive Fields	416	(1)
Responses of Simple Cells	416	(2)
Synthesis of the Simple Receptive Field	418	(1)
Responses of Complex Cells	419	(1)
Synthesis of the Complex Receptive Field	420	(1)
Receptive Fields: Units for Form Perception	421	(6)
Functional Architecture of the Visual Cortex	427	(20)
Ocular Dominance Slabs and Orientation Columns	428	(4)
Orientation Columns	429	(2)
The Relation between Ocular Dominance and Orientation Columns	431	(1)
Parallel Processing of Form, Motion, and Color	432	(7)
Magnocellular, Paravocellular, and Koniocellular ``Channels''	432	(1)
Cytochrome Oxidase Blobs and Stripes	432	(1)
Projections to Visual Area 2 (V2)	432	(1)
Association Areas of Visual Cortex	433	(1)
Motion Detection and Area MT	434	(1)
Area MT and Visual Tracking	434	(1)
Color Vision	435	(1)
Pathways to Color Vision	436	(1)
Color Constancy	437	(2)
The Integration of Visual Information	439	(3)
Horizontal Connections within Primary Visual Cortex	439	(1)
Receptive Fields from Both Eyes Converging on Cortical Neurons	440	(2)
Connections for Combining Right and Left Visual Fields	442	(1)
Where Do We Go from Here?	442
Functional Imaging	442	(1)
Faces and Letters	443
Color Constancy	438	(6)
Corpus Callosum	444	(3)
Cellular Mechanisms of Motor Control	447	(32)
The Motor Unit	449	(4)
Synaptic Inputs to Motoneurons	449	(1)
Unitary Synaptic Potentials in Motoneurons	450	(1)
The Size Principle and Graded Contractions	451	(2)
Spinal Reflexes	453	(3)
Reciprocal Innervation	453	(1)
Sensory Information from Muscle Receptors	454	(1)
Efferent Control of Muscle Spindles	455	(1)
Flexor Reflexes	456	(1)
Generation of Coordinated Movement	456	(6)
Central Patterns Generators	457	(1)
Locomotion	458	(1)
The Interaction of Sensory Feedback and Central Motor Programs	459	(1)
Respiration	459	(3)
The Organization of Motor Pathways	462	(2)
Organization of Spinal Motoneurons	462	(1)
Supraspinal control of Motoneurons	462	(1)
Lateral Motor Pathways	463	(1)
Medial Motor Pathways	463	(1)
Motor Cortex and the Execution of Voluntary Movement	464	(4)
Association Motor Cortex	465	(1)
The Activity of Cortical Neurons	466	(1)
Cortical Cell Activity Related to Direction of Arm Movements	467	(1)
Planning a Movement	468	(1)
The Cerebellum	468	(5)
Connections of the Cerebellum	469	(1)
Cytoarchitecture of the Cerebellar Cortex	470	(1)
Cellular Activity in Cerebellar Nuclei	471	(1)
Deficits in Patients with Cerebellar Damage	472	(1)
The Basal Ganglia	473
Functional Circuitry of the Basal Ganglia	473	(1)
Cellular Activity in Basal Ganglia	474	(1)
Diseases of the Basal Ganglia	474
Extracellular Recording of Motor Activity	465	(14)
PART 4 Development of the Nervous System
Development of the Nervous System	479	(46)
Terminology	480	(1)
Genetic Approaches for Understanding Development	480	(1)
Early Neural Morphogenesis	481	(4)
Production of Neuronal and Glial Cell Precursors	482	(1)
Migration of Neurons in the CNS	483	(1)
Extracellular Matrix Adhesion Proteins and Neural Crest Cell Migration	484	(1)
Regional Specification of Neural Tissue	485	(3)
Homeotic Genes and Segmentation	485	(2)
Notochord and Floor Plate	487	(1)
General Scheme for Regional Specification	488	(1)
Determination of Neuronal and Glial Cell Identity	488	(9)
Cell Lineage and Inductive Interactions in Simple Nervous Systems	488	(1)
Inductive Interactions in Development of Drosophila Eyes	489	(1)
Cell Lineage in the Mammalian CNS	489	(2)
The Relationship between Neuronal Birthday and Cell Fate	491	(2)
Genetic Abnormalities of Cortical Layers in Reeler Mice	493	(1)
Influence of Local Cues on Cortical Architecture	494	(1)
Hormonal Control of Development	494	(1)
Neural Stem Cells	494	(1)
Control of Neuronal Phenotype in the Peripheral Nervous System	495	(1)
Transmitter Choice in the Peripheral Nervous System	495	(2)
Axon Outgrowth	497	(3)
Growth Cones, Axon Elongation, and the Role of Actin	497	(2)
Cell and Extracellular Matrix Adhesion Molecules and Axon Outgrowth	499	(1)
Axon Guidance	500	(6)
Target-dependent and Target-independent Navigation	501	(1)
Navigation via Guidepost Cells	501	(1)
Synaptic Interactions with Guidepost Cells	501	(1)
Mechanisms of Axon Guidance	502	(1)
Growth Cone Navigation in the Spinal Cord	503	(2)
Semaphorin Family of Chemorepellents	505	(1)
Modulation of Response to Chemorepellents and Chemoattractants	506	(1)
Target Innervation	506	(1)
Synapse Formation	506	(6)
Accumulation of ACh Receptors	507	(1)
Agrin-induced Synaptic Differentiation	508	(3)
Formation of CNS Synapses	511	(1)
Growth Factors and Survival of Neurons	512	(4)
Nerve Growth Factor	512	(1)
Uptake and Retrograde Transport of NGF	512	(2)
The Neurotrophin Family of Growth Factors	514	(1)
Neurotrophins in the CNS	514	(1)
Neurotrophin Receptors	515	(1)
Competitive Interactions during Development	516	(4)
Neuronal Cell Death	516	(1)
Pruning and the Removal of Polyneuronal Innervation	517	(2)
Neuronal Activity and Synapse Elimination	519	(1)
Neurotrophins and Pruning	520	(1)
General Considerations of Neural Specificity	520
Discovery of Nerve Growth Factors	513	(12)
Denervation and Regeneration of Synaptic Connections	525	(24)
Changes in Axotomized Neurons and the Surrounding Glial Cells	526	(2)
Wallerian Degeneration	526	(1)
Retrograde Trans-synaptic Effects of Axotomy	527	(1)
Trophic Substances and the Effects of Axotomy	528	(1)
Effects of Denervation on Postsynaptic Cells	528	(8)
The Denervated Muscle Membrane	528	(1)
Appearance of New ACh Receptors after Denervation or Prolonged Inactivity of Muscle	528	(1)
Synthesis and Degradation or Receptors in Denervated Muscle	529	(1)
Role of Muscle Inactivity in Denervation Supersensitivity	530	(2)
Role of Calcium in Development of Supersensitivity in Denervated Muscle	532	(1)
Neural Factors Regulating ACh Receptor Synthesis	532	(1)
Distribution of Receptors in Nerve Cells after Denervation	533	(1)
Susceptibility of Normal and Denervated Muscles to New Innervation	534	(1)
Supersensitivity and Synapse formation	534	(1)
Denervation-induced Axonal Sprouting	535	(1)
Regeneration in the Vertebrate Peripheral Nervous System	536	(2)
Regrowth of Severed Axons	536	(1)
Specificity of Reinnervation	537	(1)
Properties of Nerve and Muscle after Formation of Aberrant Contacts	538	(1)
Role of Basal Lamina at Regenerating Neuromuscular Synapses	538	(3)
Synaptic Basal Lamina and Formation of Synaptic Specializations	540	(1)
Identification of Agrin	540	(1)
Regeneration in the Mammalian CNS	541	(8)
Role of Glial Cells in CNS Regeneration	541	(1)
Schwann Cell Bridges and Regeneration	542	(1)
Formation of Synapses by Axons Regenerating in the Mammalian CNS	543	(1)
Regeneration in the Immature Mammalian CNS	544	(1)
Neuronal Transplants	544	(5)
Critical Periods in Visual and Auditory Systems	549	(26)
The Visual System in Newly Born Monkeys and Kittens	550	(5)
Receptive Fields and Responses Properties of Cortical Cells in Newborn Animals	550	(1)
Ocular Dominance Columns in Newborn Monkeys and Kittens	551	(1)
Development of Ocular Dominance Columns	552	(2)
Development of Cortical Architecture in Utero	554	(1)
Genetic Factors in the Development of Visual Circuits	554	(1)
Effects of Abnormal Experience in Early Life	555	(5)
Blindness after Lid Closure	555	(1)
Responses of Cortical Cells after Monocular Deprivation	555	(1)
Relative Importance of Diffuse Light and form for Maintaining Normal Responses	556	(1)
Morphological Changes in the Lateral Geniculate Nucleus after Visual Deprivation	556	(1)
Morphological Changes in the Cortex after Visual Deprivation	556	(1)
Critical Period of Susceptibility to Lid Closure	556	(2)
Recovery during the Critical Period	558	(2)
Requirements for Maintenance of Functioning Connections in the Visual System	560	(3)
Binocular Lid Closure and the Role of Competition	560	(1)
Effects of Strabismus (Squint)	561	(1)
Changes in Orientation Preference	562	(1)
Critical Periods in Development of Human Visual System and Clinical Implications	562	(1)
Cellular and Molecular Mechanisms of Deprivation Changes	563	(4)
Effects of Impulse Activity on Structure	563	(1)
Synchronized Spontaneous Activity in the Absence of Inputs during Development	564	(2)
Cellular Mechanisms for Plasticity of Connections	566	(1)
Trophic Molecules and the Maintenance of Connections	566	(1)
Segregation of Inputs without Competition	566	(1)
Critical Periods in the Auditory System	567	(3)
Auditory and Visual Experience in Newborn Barn Owls	567	(1)
Effects of Enriched Sensory Experience in Early Life	568	(2)
Critical Periods for Higher Functions	570	(5)
What Is the Biological Advantage of Critical Periods?	571	(4)
PART 5 Conclusion
Open Questions	575
Cellular and Molecular Studies of Neuronal Functions	576	(1)
Functional Importance of Intercellular Transfer of Materials	576	(1)
Development and Regeneration	577	(1)
Genetic Approaches to Understanding the Nerveous System	577	(1)
Sensory and Motor Integration	577	(1)
Rhythmicity	578	(1)
Input from Clinical Neurology to Studies of the Brain	578	(1)
Input from Basic Neuroscience to Neurology	579	(1)
The Rate of Progress	580	(1)
Conclusions	580
Appendix A. Current Flow in Electrical Circuits	A-1
Appendix B. Metabolic Pathways for the Synthesis and Inactivation of Low-Molecular-Weight Transmitters	B-1
Appendix C. Structures and Pathways of the Brain	C-1
Glossary	G-1
Bibliography	BB-1
Index	I-1