Year: 1977
Type: other
Abstract: Cellular Biology of Neurons is a systematic introduction to functioning of nerve cells. The book is written so as to be useful to a wide readership ranging from graduate students who are beginning to read in neural science to scientists in other fields who want to learn about one or another aspect of neuronal functioning. Each chapter summarizes principles underlying an important and active area of research; the volume is organized to emphasize the scope, the directions, and the excitement of modern cellular neurobiology. This volume is an interesting example of continuity and renewal in scientific scholarship. Its roots date to 1959 when the American Physiological Society began the publication of the Handbook of Physiology with three volumes on the nervous system entitled Neurophysiology. The Society is now revising this series and enlarging its scope — as is evident in the new title, The Nervous System. Cellular Biology of Neurons is the first volume of the new series. It will be followed by several others on the sensory systems, on the motor systems, and on higher nervous system functions. It is interesting, in retrospect, to see how the study of the nervous system has evolved in the two decades since the predecessor to the present volume was published. In 1959 neurophysiology had but recently emerged as a distinctive cellular discipline. It had accumulated an impressive body of knowledge made coherent by the ionic hypothesis developed by Hodgkin, Huxley, and Katz. The ionic hypothesis explained the resting potential, the action potential, and, as extended by Katz, Fatt, Eccles, and Kuffler, it explained chemical synaptic transmission. Moreover the usefulness of the ionic hypothesis as a general theory of the electrical properties of cell membranes did much to remove neurophysiology from its relatively isolated position within cell physiology. Whereas electrical signaling is unique to excitable cells, control of the ionic permeability of membranes is common to all cells. The impact of the ionic hypothesis on other disciplines increased the interaction between neurobiology and related biological sciences; this increased interaction in turn enriched and broadened the study of nerve cells by introducing methodologies from other disciplines into neurobiology. Thus, whereas the 1959 volume marked the end of a period of research on the biophysics of excitable membranes, the present volume marks the beginning of a new period of research on the cell and molecular biology of individual neurons and of interconnected groups of cells. The promise of this period, described in the chapters of this volume, can perhaps best be summarized as a series of bold and innovative attempts to achieve new understanding. At one extreme there has been a deeper probing into the mechanisms of excitation and synaptic transmission — gating currents, noise analysis, receptor isolation — in an attempt to analyze the channels that control ionic permeability of the electrically excitable and synaptic membranes and to assign their properties to molecular components. At the other extreme are attempts to analyze neural circuitry. Here the aim has been to delineate in morphological, biochemical, and physiological detail the wiring diagrams of various neural structures and — in the limit — to relate these wiring diagrams to behavior. The object of these approaches is to understand not only how neuronal structures operate but also how they develop and how they are modified — by experience, by learning, or by disease. Some of these areas, particularly studies of the development of the nervous system and the genetics of behavior, have benefitted greatly from an influx of colleagues with new ideas from molecular genetics. The broad interdisciplinary nature of current work on the cell biology of neurons has had many sources. One significant influence has been the early work of Stephen Kuffler on the isolated lobster and crayfish sensory neurons. Here the various regions of the neuron were visualized directly so that light microscopy, electrophysiology, and transmitter biochemistry could be used in combination to study a range of cellular problems. Kuffler's “Overview” serves as an appropriate introduction to this volume. One of the most remarkable changes in the contours of neural science has been in the analysis of the fine structure of the neuron. The earlier Handbook did not consider ultrafine structure of neurons since little information was available in this area in 1959. Now observation of the structural components of neural action is central to an understanding of cellular function and particularly of synaptic level transmissions. Moreover, by using electron-microscopic autoradiography following exposure of tissue to labeled transmitter substances (or their precursors) it becomes possible, in favorable instances, to localize specific transmitters to particular species of neurons and to follow their fate within the neuron. Palay and Chan-Palay describe the recent progress in studying the morphological basis of neural action. There has also been further progress in understanding of excitation and conduction in nerve and muscle cells. These are condensed in the next section. The fundamental distinction between the passive and active properties of the membrane, first delineated in studies of anatomically simple peripheral axons, has been extended to the more complex cell body and dendritic region. Here the passive and active properties have been shown to account for the characteristic features of the two distinct types of neuronal signaling: local and long range. As a result, a new appreciation has been gained of the importance of the passive properties for integration of signals within neurons. New beginnings have also been made in analyzing the active membrane that generates the action potential. The independence of the ionic channels for Na+ and K+ has been revealed by selective pharmacological blocking agents, and a beginning has been made in analyzing the structure of the two classes of channels. Recently discovered gating currents offer the first clue into the molecular mechanisms that open the gates of the Na+ channels during the action potential. Further insights into the molecular rearrangements that accompany the action potential and synaptic potential have been gained from light-scattering and birefringence studies. The active transport mechanism responsible for establishing and maintaining the ionic gradient for Na+ and K+ has been further studied. For example, using labeled ouabain (a selective inhibitor of the Na+–K+ transport mechanisms) the density and distribution in the membrane of the transport molecules have been analyzed. Particularly important is the finding, in a variety of systems, that the Na+–K+ transport is electrogenic and can participate in signaling. In some cells the Na+–K+ transport generates a component (up to 30%) of the resting potential; in other cells it contributes to the posttetanic hyperpolarizing afterpotentials. The ultimate achievement for a molecular understanding of excitable membranes is to reconstruct the membrane from component molecular parts. There is understandable excitement therefore in the finding that artificial lipid membranes show excitable characteristics when treated with agents that endow them with the properties of ion-specific ionophores. These advances in the biology of excitable membranes are discussed in the chapters by Rall, Hille, Cohen and De Weer, and Finkelstein and Mauro. Progress has not been limited to nerve. Costantin reviewed the combined morphological, biochemical, and electrophysiological studies of muscle that have provided us with a detailed model of muscle function, the sliding filament hypothesis. He also described the role of the sarcoplasmic reticulum and the transverse tubular system in mediating the signals that couple excitation to contraction. One of the most fertile areas of research has been in synaptic transmission. Two classes of synapses, chemical and electrical, can now be clearly distinguished on both morphological and functional grounds. A variety of substances — all amino acids or closely related small molecules — have been shown to function as transmitter substances at chemical synapses. These substances include acetylcholine, norepinephrine, serotonin, dopamine, gamma aminobutynic acid, glutamate, and glycine. They are thought to be packaged in vesicles and released from the vesicle in an all-or-none (quantal) fashion in which the entire contents are extruded. Combined electrophysiological, morphological, and biochemical studies are now testing the vesicular hypothesis of quantal transmission and examining the life cycle of the synaptic vesicle and its contents. The fourth section reviews these new studies on synaptic transmission. Heuser and Reese analyze the evidence favoring a fusion of the vesicle with terminal membrane after exocytosis of transmitter and recycling of the vesicle membrane. Takeuchi and Martin review new approaches to the study of the electrophysiology of receptors (including the use of ultrafine micro-electrodes for resolving receptor distribution on a micron scale) and of transmitter release, which have allowed these processes to be examined quantitatively. Bennett describes the physiological and morphological features of electrical synapses, contrasting them with chemical synapses, and Holman and Hirst describe the common and unique features of the synapses made by neurons of the autonomic nervous system. The chapters by Collier, by Geffen and Jarrott, by Gershon, and by Obata detail the advances in the understanding of the biochemistry of the beststudied transmitter compounds: acetylcholine, norepinephrine, serotonin, gamma aminobutyric acid, and glutamate. Maelicke, Fulpius, and Reich review the isolation and partial characterization of the acetylcholine receptor. Mason and Bern consider the mechanisms of neurosecretion — the process whereby nerve cells secrete hormones into the general circulation. Grafstein discusses the transport of transmitters and other molecules, large and small, which move from the cell body along the axon to the synaptic terminal. One of the most intriguing new developments in the study of neuronal function concerns the questions: What are the steps in neuronal differentiation? How do neurons seek one another out and how do they form specific synaptic connections appropriate for behavioral functions? How are these connections maintained? These questions are raised and considered in the chapters grouped under the heading Cellular Interactions. Fischbach and Nelson describe neuronal differentiation and synapse formation in tissue culture. Rosenthal analyzes how interactions between nerve cells or between nerve and muscle lead to functional and biochemical alteration in the interacting elements. Grinnell considers factors that determine the specificity in the interconnections between neurons. The properties of glial cells and their function in neuronal interactions are reviewed by Orkand. Success in studying individual nerve cells and peripheral synapses has encouraged investigators to apply the techniques of cell biology to the study of systems of neurons within the central nervous system. The goal here is to work out in morphological, biochemical, and functional detail the precise patterns of interconnections between cells and their mode of synaptic interaction. In the section entitled Systems of Neurons, Burke and Rudomin, Shepherd, and Spencer describe focal areas in which this approach has been successful: the spinal cord, the olfactory bulb, and the cerebral and cerebellar cortices. Studies in these areas have revealed a number of major insights into neuronal functioning including neurons that do not generate action potentials, neurons with multiple trigger zones, and various types of local dendrodendritic interactions. A final goal of the cell biology of neurons is to understand how the sensory and motor systems are organized, and how the neuronal circuits of behavior are modified by learning. The chapters by Kennedy and Davis, Wiersma and Roach, and Kandel address these questions using examples from studies on invertebrate nervous systems. These studies illustrate the power that cellular techniques have brought to bear on the study of behavior and the impact on psychology that the insights emerging from this research have had. The strength of the volume resides in the excellent reviews written by the authors, for which I thank each of them. I am particularly pleased to have Leroy Costantin's chapter. His early death at age 39, on November 7, 1974, was a great loss to all who have known him and his work. Costantin's contribution — of which his review is a beautiful example — embodies the perspective, vitality, and critical sense that characterize the best among the younger generation in our field. I have been greatly helped in every phase of editing this volume by John M. Brookhart and Vernon B. Mountcastle, the section editors for the volumes on The Nervous System. It is with pleasure that I acknowledge my debt to them. I am also grateful to Kathleen K. Lamar, the copy editor for this volume, to Elspeth M. Root who with the help of Catherine B. Carlston and Brenda B. Rauner read the galleys and completed the production of the volume, and to my secretary, Sally Muir, who helped in the seemingly endless task of rounding up the last few stray black sheep.
Source: Comprehensive physiology
Author: Eric R. Kandel
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4236081773