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 higher-level 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 decision-making 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.