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Principles of Neural Science, Sixth Edition

Principles of Neural Science, Sixth Edition PDF

Author: Eric Kandel

Publisher: McGraw-Hill Education


Publish Date: March 29, 2021

ISBN-10: 1259642232

Pages: 1696

File Type: PDF

Language: English

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Book Preface

As in previous editions, the goal of this sixth edition  of Principles of Neural Science is to provide readers with  insight into how genes, molecules, neurons, and the  circuits they form give rise to behavior. With the exponential growth in neuroscience research over the 40 years  since the first edition of this book, an increasing challenge is to provide a comprehensive overview of the field  while remaining true to the original goal of the first  edition, which is to elevate imparting basic principles  over detailed encyclopedic knowledge.
Some of the greatest successes in brain science over  the past 75 years have been the elucidation of the cell  biological and electrophysiological functions of nerve  cells, from the initial studies of Hodgkin, Huxley, and  Katz on the action potential and synaptic transmission to our modern understanding of the genetic and  molecular biophysical bases of these fundamental processes. The first three parts of this book delineate these remarkable achievements.

The first six chapters in Part I provide an overview  of the broad themes of neural science, including the  basic anatomical organization of the nervous system  and the genetic bases of nervous system function and  behavior. We have added a new chapter (Chapter 5) to  introduce the principles by which neurons participate  in neural circuits that perform specific computations  of behavioral relevance. We conclude by considering  how application of modern imaging techniques to the  human brain provides a bridge between neuroscience  and psychology. The next two parts of the book focus  on the basic properties of nerve cells, including the  generation and conduction of the action potential  (Part II) and the electrophysiological and molecular  mechanisms of synaptic transmission (Part III).

We then consider how the activity of neurons in  the peripheral and central nervous systems gives rise  to sensation and movement. In Part IV, we discuss the  various aspects of sensory perception, including how  information from the primary organs of sensation is  transmitted to the central nervous system and how it  is processed there by successive brain regions to generate a sensory percept. In Part V, we consider the neural  mechanisms underlying movement, beginning with  an overview of the field that is followed by a treatment  ranging from the properties of skeletal muscle fibers  to an analysis of how motor commands issued by the  spinal cord are derived from activity in motor cortex and cerebellum. We include a new treatment that  addresses how the basal ganglia regulate the selection  of motor actions and instantiate reinforcement learning (Chapter 38).
In the latter parts of the book, we turn to higherlevel cognitive processes, beginning in Part VI with a  discussion of the neural mechanisms by which subcortical areas mediate homeostatic control mechanisms, emotions, and motivation, and the influence of  these processes on cortical cognitive operations, such  as feelings, decision-making, and attention. We then  consider the development of the nervous system in  Part VII, from early embryonic differentiation and the  initial establishment of synaptic connections, to their  experience-dependent refinement, to the replacement  of neurons lost to injury or disease. Because learning  and memory can be seen as a continuation of synaptic development, we next consider memory, together  with language, and include a new chapter on decisionmaking and consciousness (Chapter 56) in Part VIII.

Finally, in Part IX, we consider the neural mechanisms  underlying diseases of the nervous system. Since the last edition of this book, the field of  neuroscience has continued to rapidly evolve, which  is reflected in changes in this edition. The continued  development of new electrophysiological and light  microscopic–based imaging technologies has enabled  the simultaneous recording of the activity of large populations of neurons in awake behaving animals. These  large data sets have given rise to new computational  and theoretical approaches to gain insight into how  the activity of populations of neurons produce specific behaviors. Light microscopic imaging techniques using genetically encoded calcium sensors allow us to  record the activity of hundreds or thousands of defined  classes of neurons with subcellular resolution as an  animal engages in defined behaviors. At the same time,  the development of genetically encoded light-activated  ion channels and ion pumps (termed optogenetics) or  genetically engineered receptors activated by synthetic  ligands (termed chemogenetics or pharmacogenetics)  can be used to selectively activate or silence genetically defined populations of neurons to examine their  causal role in such behaviors. In addition to including such material in chapters throughout the book,  we introduce some of these developments in the new  Chapter 5, which considers both the new experimental technologies as well as computational principles by  which neural circuits give rise to behavior. Over the past 20 years, there has also been an expansion of new technologies that enable noninvasive and  invasive recordings from the human brain. These studies  have narrowed the gap between neuroscience and psychology, as exemplified in the expanded discussion of  different forms of human memory in Chapter 52. Noninvasive brain imaging methods have allowed scientists  to identify brain areas in humans that are activated during cognitive acts. As discussed in a new chapter on the  brain–machine interface (Chapter 39), the implantation  of electrodes in the brains of patients permits both electrophysiological recordings and local neural stimulation,  offering the promise of restoring some function to individuals with damage to the central or peripheral nervous system.

An understanding of basic and higher-order  neural mechanisms is critical not only for our understanding of the normal function of the brain, but also  for the insights they afford into a range of inherited  and acquired neurological and psychiatric disorders.  With modern genetic sequencing, it is now clear that  inherited or spontaneous mutations in neuronally  expressed genes contribute to brain disease. At the
same time, it is also clear that environmental factors  interact with basic genetic mechanisms to influence  disease progression. We now end the book with a new  section, Part IX, which presents the neuroscientific  principles underlying disorders of the nervous system.  In previous editions, many of these chapters were dispersed throughout the book. However, we now group  these chapters in their own part based on the increasing appreciation that the underlying causes of what  appear to be separate diseases, including neurodegenerative diseases, such as Parkinson and Alzheimer  disease, and neurodevelopmental disorders, such as  schizophrenia and autism, share certain common principles. Finally, these chapters emphasize the historical  tradition of how studies of brain disease provide deep  insights into normal brain function, including memory  and consciousness.

In writing this latest edition, it is our hope and  goal that readers will emerge with an appreciation  of the achievements of modern neuroscience and the  challenges facing future generations of neuroscientists. By emphasizing how neuroscientists in the past  have devised experimental approaches to resolve  fundamental questions and controversies in the field,  we hope that this textbook will also encourage readers to think critically and not shy away from questioning received wisdom, for every hard-won truth  likely will lead to new and perhaps more profound  questions in brain science. Thus, it is our hope that  this sixth edition of Principles of Neural Science will  provide the foundation and motivation for the next generation of neuroscientists to formulate and investigate these questions


We were most fortunate to have had the creative editorial assistance of Howard P. Beckman, who passed away  earlier this year after having finished his work on this  edition. Following graduation from San Francisco State  University with a BA in 1968, Howard began his distinguished career as a scientific editor. In 1997, he received  a law degree from John F. Kennedy University and began  a parallel career in environmental law. Howard has been  an integral part of Principles of Neural Science since the  third edition. Although he was not trained as a scientist,  his logical thinking and rigorous intellect helped ensure  that the book had a unified style of exposition. Howard’s  demand for clarity of writing has had an immeasurable  impact on each edition of this book, and he will be greatly  missed by all who worked with him over the years.
We owe an enormous debt of gratitude to Pauline  Henick, who skillfully managed the editorial project with  great care, keen intelligence, and the utmost diligence.  Pauline somehow managed with good humor and  understanding to keep all of the editors and authors  of the book on track with their chapters through some  very difficult circumstances. The timely publishing of  the book would not have been possible without her  stellar contributions.

We also wish to thank Jan Troutt of Troutt Visual  Services for her superb technical and artistic contributions to the illustrations. We appreciate the artistic  expertise and keen eye of Mariah Widman, who helped  with the preparation of the figures.  We are indebted to our colleagues at McGraw  Hill—Michael Weitz, Kim Davis, Jeffrey Herzich, and  Becky Hainz-Baxter—for their invaluable help in the  production of this edition. Anupriya Tyagi, Cenveo  Publisher Services, did an outstanding job of overseeing the composition of the book, for which we are most  grateful.

Many other colleagues have helped the editors  by critically reading selected chapters of the book and  have helped the authors with assistance in the research  and writing of the chapters. We wish to acknowledge  the contributions of Katherine W. Eyring to Chapter 15;  Jeffrey L. Noebels, MD, PhD, to Chapter 58; and Gabriel  Vazquez Velez, PhD, Maxime William C. Rousseaux,  PhD, and Vicky Brandt to Chapter 63.

We also wish to acknowledge the important role  of authors of chapters in previous editions of Principles  of Neural Science, whose past contributions continue to  be reflected in a number of chapters in the present edition. These legacy authors include Cori Bargmann, Uta  Frith, James Gordon, A.J. Hudspeth, Conrad Gilliam,  James E. Goldman, Thomas M. Jessell (deceased), Jane  M. Macpherson, James H. Schwartz (deceased), Thomas  Thach (deceased), and Stephen Warren.  We are especially indebted to the editors of the different sections (parts) of the book—Thomas D. Albright,  Randy M. Bruno, Thomas M. Jessell (deceased), C. Daniel  Salzman, Joshua R. Sanes, Michael N. Shadlen,  Daniel M. Wolpert, and Huda Y. Zoghbi—who played  a critical role in planning the overall organization of  their sections and working with the authors to shape  their chapters. Most importantly, we owe the greatest  debt to the contributing authors of this edition. We finally thank our spouses and families for their  support and forbearance during the editorial process

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