Table of Contents

Part I. Introduction to the Nervous System

1. Principles of Signaling and Organization


*Introductory material

*Increased emphasis on genetics and molecular mechanisms




2. Signaling in the Visual System


*Shifted to the beginning of the book from the end

*Extensively reworked to improve accessibility for readers without background knowledge of neurobiology

*Synaptic physiology in the visual cortex




3. Functional Architecture of the Visual Cortex
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*Like Chapter 2, shifted to the beginning of the book

*New information about columnar organization




Part II. Electrical Properties of Neurons and Glia

4. Ion Channels and Signaling


*Minor revisions for increased clarity




5. Structure of Ion Channels
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*Detailed molecular structure of both the nicotinic acetylcholine receptor channel and the voltage-sensitive potassium channel

*Conformational changes underlying channel gating

*Regulation of ion selectivity

*Updated catalogue of ion channels and channel subunits, including revised protein and gene designations




6. Ionic Basis of the Resting Potential


*Channels associated with â$e leakâ$e currents in the resting membrane




7. Ionic Basis of the Action Potential


*Mechanism underlying voltage gating of channels

*Mechanisms underlying hyperpolarizing and depolarizing after potentials

*Role of afterpotentials in membrane excitability




8. Electrical Signaling in Neurons


*Revised discussion of membrane resistance and capacitance

*Detailed structure of gap junctions




9. Ion Transport across Cell Membranes


*Revised discussion of chloride transport

*Updated classification and designation of neurotransmitter transporters

*Expanded discussion of transmitter uptake mechanisms




10. Properties and Functions of Neuroglial Cells
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*The role of glia at synapses

*Radial glia and neurogenesis

*Calcium waves in glia

*Regulation of cerebral blood flow by glia

*The role of microglia




Part III. Intercellular Communication

11. Mechanisms of Direct Synaptic Transmission


*Updated content on gating of nicotinic acetylcholine receptors

*Discussion of chemical transmission expanded to include excitatory and inhibitory transmission in the mammalian central nervous system

*New material on drugs and toxins acting on the neuromuscular junction, and on how transmitter receptors are localized at their postsynaptic sites

*Expanded treatment of the role of connexons and the functions of electrical transmission in the mammalian central nervous system




12. Indirect Mechanisms of Synaptic Transmission


*New material on how G proteins work

*Discussion of the role of membrane phospholipids as ion channel regulators

*New coverage of endocannabinoids, nitric oxide, and carbon monoxide as neural messengers

*New material on how different receptor-activated signaling cascades are integrated or segregated in the neuron




13. Release of Neurotransmitters
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*New evidence for the direct role of calcium in transmitter release

*Use of fluorescent dyes and capacitance measurements to monitor vesicle fusion

*Detailed mechanism of vesicle fusion and exocytosis

*Molecular details of active zone structure revealed by electron tomography

*Structure of ribbon synapses

*The role of vesicle pools in transmitter release and recovery




14. Neurotransmitters in the Central Nervous System
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*Expanded and updated sections on amino acid transmitters, acetycholine, monoamines, and ATP

*Coverage of new aspects of peptidergic transmission: nociceptin (orphanin); the orexins, sleep, and regulation of food intake; and vasopressin, oxytocin, and the social brain




15. Transmitter Synthesis, Transport, Storage, and Inactivation


*New material on co-uptake, co-storage, and co-release of transmitters




16. Synaptic Plasticity


*Expanded discussion of presynaptic and postsynaptic mechanisms underlying long-term potentiation and long-term depression




Part IV. Integrative Mechanisms

17. Autonomic Nervous System


*Retinal ganglion cells responding to light

*Circadian rhythms

*M current second messengers

*Leptins




18. Cellular Mechanisms of Behavior in Ants, Bees, and Leeches


*Path-finding by ants on stilts

*Optical recording and systems approach to behavioral analysis; how a leech makes up its mind




Part V. Sensation and Movement

19. Sensory Transduction
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*Fundamental aspects of sensory signaling exemplified by cutaneous and muscle receptors

*Detailed and updated descriptions of hair cell mechanotransduction, chemical senses, and nociception




20. Transduction and Transmission in the Retina
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*Coverage of the transduction cascade whereby the absorption of light results in photoreceptor hyperpolarization

*How intrinsically photosensitive ganglion cells subserve circadian rhythms

*Synaptic connectivity of photoreceptors, interneurons, and ganglion cells in the retina




21. Touch, Pain, and Texture Sensation
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*Completely new chapter, covering the most recent research on the somatosensory system from receptors to cortical organization

*Description of the processing that leads from contact of an object with the skin to recognition of the physical properties of that object

*New material on the functional organization of the somatosensory system, both in rats and mice, where the whiskers are particularly important, and in primates, where the fingertips are particularly important




22. Auditory and Vestibular Sensation
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*Frequency selectivity and amplification in the mammalian cochlea

*Electrical tuning of hair cells in the turtle inner ear

*Structure and function of the vestibular periphery




23. Constructing Perception
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*Completely new chapter, dedicated to a description of processing in the brain that occurs after the primary sensory areas

*Special attention given to current investigations concerning how a vibration on the fingertip is perceived, and how objects are recognized in a visual scene




24. Circuits Controlling Reflexes, Respiration, and Coordinated Movements


*Optical recording from brainstem respiratory circuits

*Columnar organization of motor cortex

*Posture




Part VI. Development and Regeneration of the Nervous System

25. Development of the Nervous System


*Text now includes, among many other additions: homeotic genes for forebrain development; neuron generation from radial glia; considerations of adult neurogenesis; mention of clinically important developmental defects

*Broadened overview of signaling




26. Critical Periods in Sensory Systems


*The role of experience in shaping connectivity of the visual cortex

*Critical periods in auditory system development

*The interplay of intrinsic and extrinsic factors in developmental plasticity




27. Regeneration of Synaptic Connections after Injury


*Greater emphasis on molecular mechanisms of synapse formation, agrin receptors, and the potential for use of stem cells for repair of the central nervous system




Part VII. Conclusion

28. Open Questions


*Clinical relevance emphasized




Appendices


*Current Flow in Electrical Circuits

*Metabolic Pathways for the Synthesis and Inactivation of Low-Molecular-Weight Transmitters

*Structures and Pathways of the Brain

About the Author

John G. Nicholls is Professor of Neuroscience at the International School for Advanced Studies in Trieste (known as SISSA). He was born in London in 1929 and received a medical degree from Charing Cross Hospital and a Ph.D. in physiology from the Department of Biophysics at University College London, where he did research under the direction of Sir Bernard Katz. He has worked at University College London, at Oxford, Harvard, Yale, and Stanford
Universities, and at the Biocenter in Basel. With Stephen Kuffler, he made experiments on neuroglial cells and wrote the first edition of this book. He is a Fellow of the Royal Society, a member of the Mexican Academy of
Medicine, and the recipient of the Venezuelan Order of Andres Bello. He has given laboratory and lecture courses in neurobiology at Woods Hole and Cold Spring Harbor, and in universities in Asia, Africa, and Latin America. His work concerns regeneration of the nervous system after injury and mechanisms that give rise to the respiratory rhythm.

A. Robert Martin is Professor Emeritus in the Department of Physiology at the University of Colorado School of Medicine. He was born in Saskatchewan in 1928 and majored in mathematics and physics at the University of Manitoba. He received a Ph.D. in Biophysics in 1955 from University College London, where he worked on synaptic transmission in mammalian muscle under the direction of Sir Bernard Katz. From 1955 to 1957 he did postdoctoral research in the laboratory of Herbert
Jasper at the Montreal Neurological Institute, studying the behavior of single cells in the motor cortex. He has taught at McGill University, the University of Utah, Yale University, and the University of Colorado Medical
School, and has been a visiting professor at Monash University, Edinburgh University, and the Australian National University. His research has contributed to the understanding of synaptic transmission, including the mechanisms of transmitter release, electrical coupling at synapses, and properties of postsynaptic ion channels.

Paul A. Fuchs is Director of Research and the John E. Bordley Professor of Otolaryngology-Head and Neck Surgery, Professor of Biomedical Engineering, Professor of Neuroscience and co-Director of the Center for Sensory Biology at the Johns Hopkins University School of Medicine. Born in St. Louis, Missouri in 1951, Fuchs graduated in biology from Reed College in 1974. He received a Ph.D. in Neuro- and Biobehavioral Sciences in 1979 from Stanford University where he investigated
presynaptic inhibition at the crayfish neuromuscular junction under the direction of Donald Kennedy and Peter Getting. From 1979 to 1981 he did postdoctoral research with John Nicholls at Stanford University, examining
synapse formation by leech neurons. From 1981 to 1983 he studied the efferent inhibition of auditory hair cells with Robert Fettiplace at Cambridge University. He has taught at the University of Colorado and the Johns Hopkins University medical schools. His research examines excitability and synaptic signaling of sensory hair cells and neurons in the vertebrate inner ear.

David A. Brown is Professor of Pharmacology in the Department of Neuroscience, Physiology, and Pharmacology at University College London. He was born in London in 1936 and gained a B.Sc. in Physiology from University College London and a Ph.D. from St. Bartholomew's Hospital Medical College ("Barts") studying transmission in sympathetic ganglia. He then did a post-doc at the University of Chicago, where he helped design an integrated neurobiology course for graduate medical
students. He has since chaired departments of Pharmacology at the School of Pharmacy and at University College in London, and has also worked in several labs in the United States, including the Department of Physiology
and Biophysics at the University of Texas in Galveston, and as Fogarty Scholar-in-Residence at NIH in the labs of Mike Brownstein, Julie Axelrod, and Marshall Nirenberg. At Galveston, he and Paul Adams discovered the M-type potassium channel, which provided new insight into how neurotransmitters could alter nerve cell activity by regulating a voltage-gated ion channel. He continues to work on the regulation of ion channels by G protein-coupled receptors. He is a Fellow of the Royal Society, a
recipient of the Feldberg Prize, and has an Honorary Doctorate from the University of Kanazawa in Japan.

Mathew E. Diamond, like John Nicholls, is Professor of Cognitive Neuroscience at the International School for Advanced Studies in Trieste (SISSA). He earned a Bachelor of Science degree in Engineering from the University of Virginia in 1984 and a Ph.D. in Neurobiology from the University of North Carolina in 1989. Diamond was a postdoctoral fellow with Ford Ebner at Brown University and then an assistant professor at Vanderbilt University before moving to SISSA to found the
Tactile Perception and Learning Laboratory in 1996. His main interest is to specify the relationship between neuronal activity and perception. The research is carried out mostly in the tactile whisker system in rodents,
but some experiments attempt to generalize the principles found in the whisker system to the processing of information in the human tactile sensory system.

David A. Weisblat is Professor of Cell and Developmental Biology in the Department of Molecular and Cell Biology at the University of California, Berkeley. He was born in Kalamazoo, Michigan in 1949, studied biochemistry as an undergraduate with Bernard Babior at Harvard College, where he was introduced to neurobiology in a course led by John Nicholls, and received his Ph.D. from Caltech for studies on the electrophysiology of Ascaris in 1976 with Richard Russell. He
began studying leech development with Gunther Stent in the Department of Molecular Biology at Berkeley and was appointed to the Zoology Department there in 1983. As a postdoc, he developed techniques for cell lineage tracing by
intracellular microinjection of tracer molecules. Current research interests include the evolution of segmentation mechanisms, D quadrant specification, and axial patterning. Work from his laboratory has helped to establish the leech Helobdella as a tractable representative of the super-phylum Lophotrochozoa, for the study of evolutionary developmental biology. He has assisted or organized courses in Africa, India, Latin America, and at Woods Hole, Massachusetts.