The Brain as a Chemical Machine

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.
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. Jean-Pierre Changeux
is honorary professor at the Collège de France and at the Institut Pasteur, a
member of the French Academy of Sciences. In addition to L’Homme neuronal
[Neuronal Man] he is the author of Raison et Plaisir and L’Homme de vérité. He
is also co-author, with Alain Connes, of Matière à penser [Conversations on
Mind, Matter, and Mathematics] and, with Paul Ricœur, of La Nature et la Règle
[What Makes Us Think?]. All thought-provoking works. Stuart J. Edelstein is
Professor of Biochemistry at the University of Geneva and a foreign associate
member of the Academy of Sciences. "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
fonction 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 Medecine -
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 in Chemistry - ISIS-Université Louis Pasteur, Strasbourg "The
human brain is as much a chemical as an electrical network. Its intricacy and
sophistication set it apart from any known technical device. The
groundbreaking papers by Monod, Jacob, Wyman, and Changeux in the 1960s on
chemical regulation and control were eye-opening for all us who were doing
experimental research in ths 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 its 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
thse 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 “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 fortcheat 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
sub- unit 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 effortful 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
schiz- ophrenia—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