"This book is unlike any recent scientific book. It is more like a forty-year

research meeting in one of the world's most creative neurobiology laboratories-an

intellectual tour de force that surveys the developmental

trends and achievements of twentieth-century neuroscience in molecular,

structural, and functional terms. The book therefore becomes an

extraordinary educational saga, moving from Sir Henry Dale's pharmacology

of nicotine to genetic diseases involving mutations of the cation

channel function of nicotinic acetylcholine receptors. Research into

these archetypal proteins has been carried out by pharmacologists,

biochemists, molecular biologists, electrophysiologists, behavioral

scientists, and geneticists, with Jean-Pierre Changeux and his coworkers

participating in every aspect of this remarkable inquiry.

Nicotinic acetylcholine receptors are the workhorse of the fast actions of

the chemical signal acetylcholine, abundantly transmitted in both the

peripheral and the central nervous system. Thanks to their variable subunit

composition they come in many flavors, mediating control of voluntary

muscles in the periphery and helping to regulate reward functions,

cognition, and memory in the brain. This rich functionality leads the

authors to describe models of neuromuscular junction development as

well a global workspace model of cognitive function and its role in effort-ful

learning.

The nicotinic acetylcholine receptor was among the first ligand-gated

ion channels to be sequenced and studied by patch-clamp methods. It

has been the object of neurobiological research in England, France,

Germany, Japan, and the United States, with contributions of equal

weight being made by many teams of researchers over a number of

decades, all carefully chronicled and explained by the authors. This book

is to be highly recommended to young scientists who want to discover

into how many fields a single protein molecule can take them-from

snake venom action to myasthenia gravis, addiction, learning, and schizophrenia-if

they are willing patiently to learn new research techniques

rather than specialize in a single method or instrument.

To investigate the nicotinic acetylcholine receptor in all its aspects

requires a Renaissance mind, and it is exactly this that Changeux and

Edelstein have brought to bear on one of the most studied topics in

neuroscience of the last century."

Tamas Bartfai, Chair and Professor, Department of Neuropharmacology

The Scripps Research Institute

"The nicotinic acetylcholine receptor has served for many

decades as the prototype for neurotransmitter receptors.

Acetylcholine was the first neurotransmitter shown to be

involved in the function of the mammalian brain and its

nicotinic receptor the first receptor to be characterized.

Jean-Pierre Changeux is the indisputable pioneer in this field.

This volume summarizes with great lucidity the history of a

highly important topic in neuroscience."

Paul Greengard, Nobel laureate in Medicine

The Rockefeller University

"From the molecule to thought itself-an extraordinary journey!

Changeux and Edelstein are uniquely qualified to relate this

utterly fascinating story, whose philosophical implications are

no less important than the scientific research underlying them."

Jean-Marie Lehn, Nobel laureate la Chemistry

ISIS-Université Louis Pasteur, Strasbourg

"The human brain is as much a chemic al as an electrical

network. Its intricacy and sophistication set it apart from

any known technical device. The groundbreaking papers by

Monod, Jacob, Wyman, and Changeaux in the 1960s on chemical

regulation and control were eye-opening for all of us who

were doing experimental research in this field, and they have

turned out to be crucial for understanding biological evolution

and learning in a broad sense. Since then Changeux

and Edelstein have achieved international fame for their work

on nicotinic acetylcholine receptors, amply documented in

this masterful account."

Manfred Eigen, Nobel laureate in Chemistry

Max Planck Institute for Biophysical Chemistry, Göttingen

"One hesitates to call this book a monograph, for despite ils

comprehensive treatment of a complex subject it is not meant

solely for specialized readers. In concentrating on a single

class of neuroreceptors, the nicotinic acetylcholine receptor,

it seeks to draw out general principles which apply more

widely. It will therefore be welcomed not only by serious

workers and students in the field of neurobiology, but also by

anyone interested in the broader field of neuroscience."

Sir Aaron Klug om frs, Nobel laureate in Chemistry

University of Cambridge

"Changeux and Edelstein have provided a concise yet highly

comprehensive account of perhaps the prototypical neurotransmitter

complex, the nicotinic acetylcholine receptor.

The story of how the roles played by this signal transduction

system in nicotine dependence, learning, memory, and the

processes of cognition came to be unraveled is an exciting

saga, both beautiful and profound. A lovely historico-scientific

document."

Floyd E. Bloom, Professor Emeritus.

The Scripps Research institute

"Changeux and Edelstein describe a classically Cartesian

process of scientific investigation that leads to a most non-Cartesian

conclusion. Having elucidated the mechanisms

of action and interaction by which the various elements that

make up the nicotinic acetylcholine receptor operate throughout

the nervous system, from neuromuscular junctions to the

brain itself, the authors turn to the role of these structures

and mechanisms in supporting cognition and giving access

to consciousness-thus parting ways with Descartes and the

view that the mind is able somehow to exist independently

of the body. A work of truly remarkable erudition and insight."

Roger Guillemin, Nobel laureate in Medicine

Salk Institute for Biological Studies

The purpose of this book is to give a clear

and straightforward account of the remarkable

properties of the nicotinic receptor for

acetylcholine, a membrane protein involved

in chemical transduction in the nervous

system that is also the target of a widely used

drug, nicotine. This molecule also happens

to be the first pharmacological receptor and

ion channel ever to have been identified.

Jean-Pierre Changeux has played a leading

role with Stuart J. Edelstein in the investigation

of nicotinic acetylcholine receptors

and allosteric proteins.

The aim of this book is not only to review

the most recent experimental and theoretical

breakthroughs in the study of the nicotinic

receptor, but also to give the reader a sense

of the intellectual excitement and adventure

that accompanied the various stages of

discovery.

The story of the receptor for acetylcholine

provides a unique perspective on the development

of a branch of science at the crossroads

of four major domains: biochemistry, neurophysiology,

pharmacology, and the behavioral

sciences.

An understanding of nicotinic receptors can

help patients suffering from a range of neurological

and psychiatric disorders, among

them Alzheimer's and Parkinson's diseases,

Tourette's syndrome, nocturnal frontal lobe

epilepsies, and possibly schizophrenic syndromes

and autism as well-to say nothing

of addiction to nicotine itself. For forty years

now the nicotinic receptor has served as

an outstanding model of signal transducers

and pharmacological receptors.

This richly illustrated volume furnishes an

exceptional opportunity for scientists and

students to follow the course of a major

advance in our understanding of the molecular

basis of brain functions.