Cholinergic Mechanisms

This volume offers a comprehensive update and overview of the field of cholinergic transmission as presented by some thirty distinguished investigators who were recruited for their task from Germany, Great Britain, Canada, USA, Sweden, Israel, France and Italy. Exciting new discoveries, described in this volume, are due to recent methodological breakthroughs. These discoveries throw new light on many areas of cholinergic mechanisms.

Much of our understanding of brain physiology has focused on what one might call, first order processes. These essentially include the primary synaptic mechanisms underlying excitation (mainly glutamate) and inhibition (mainly GABA). Our attention has focused on how the balance of excitation and inhibition regulates the timing, patterns, and extent of information flow across various circuits. A lot less is understood regarding second order processes that sculpt and modify these primary interactions. One such modulatory transmitter in the brain is acetylcholine (ACh). The importance of ACh in modulating various behaviors related to learning, memory, and attention has been recognized over the last four decades as has its involvement in various neurodegenerative and psychiatric disorders. However, our understanding of the mechanistic bases for these actions is at its infancy, at best and much remains to be understood. The array of receptor subtypes for nicotinic and muscarinic receptors, their different locations, and complex signal transduction mechanisms remain a puzzle. Transmitter (ACh) release sites and their relationship to receptor loci are poorly understood. Overall, we lack a unifying framework for conceptualizing how disparate actions of the transmitter on receptors lead to circuit modulation and, eventually, influences on cognition. By its very nature, reports on cholinergic signaling are quite scattered, presented in journals across sub-disciplines and in the context of the systems they modulate. Hence, there is need for consolidation of these studies under a single cover that would allow one to compare and contrast the effects of this transmitter across systems and contexts. This special issue represents one such compilation. The issue addresses cholinergic modulation of defined circuits that lead to specific behaviors and consists of a judicious mixture of review articles and primary papers. The articles focus on three aspects of the system: 1) Cellular targets of cholinergic signaling. 2) Receptor mechanisms. 3) Endogenous transmitter distribution and action. While no common mechanism emerges that can explain cholinergic actions on brain functions, on can postulate that the transmitter system is dynamic, modulating the balance of excitation and inhibition in various circuits. This modulation sets up timed network oscillations and it is tempting to speculate that these oscillations form a template for better encoding of afferent inputs. One can broadly envision the role of the cholinergic system as facilitating processes that allow for more efficient acquisition of learning and engraving of memories. Thus, understanding the mechanisms underlying tonic and stimulus-dependent release of ACh and how it alters firing templates of neuronal networks would be the first step towards elucidating its role in learning and memory. This special topics edition provides clues to some of the actions of ACh. It is hoped that the articles allow the reader to extract common themes and potential mechanisms of cholinergic regulation that will lead to elucidation of general principles governing the actions of this important neuromodulator.

Although serious interest in studying the role of central cho linergic processes in psychopathology is just beginning to emerge, experimental literature on the part played by cholinergic mechanisms in brain behavior. reiations is quite extensive. During the past thirty years, cholinergic research has contributed significantly to the characterization and differentiation of adaptive mechanisms in volved in input selection, perception, cortical, autonomic and behav ioral activation, learning, memory, and inhibitory control of behav ioral outputs. To say that dysfunction of one or more of these mech anisms may be at the root of neuropsychiatric illnesses such as schiz ophrenia would be stating the obvious. This book examines the part cholinergic processes might play in dysfunctions of the adaptive processes involved in higher brain func tions and their significance for the pathogenesis, classification, etiology, and treatment of psychopathological conditions. In a series of wide ranging reviews of the available information, the subject is discussed from a variety of perspectives, using data derived from both experimental and clinical research. The purpose is not so much to determine whether cholinergic excess or deficiency is causal in this or that neuropsychiatric syndrome, but rather to try to understand the disease mechanisms in terms of adaptive processes in which cholinergic systems seem to play an important part.

This volume represents a collection of papers which were contributed by participants at a Symposium for Cholinergic Mechanisms and Psycho pharmacology, held in La Jolla, California on March 28-30, 1977. The were chosen to emphasize areas in which there has been substantial topics progress in the past 2-3 years and fall into seven major groups dealingwith: cholinergiC receptors; chemistry, histochemistry and enzymology; cyclic nucleotides and cholinergiC mechanisms; storage, compartmentation and release of acetylcholine; regulatory mechanisms in acetylcholine metab olism; modulation of acetylcholine metabolism; and behavioral and clin ical manifestations of cholinergiC function and dysfunction. Each group contains one or more reviews and a number of shorter contributions de scribing current work. This symposium was the third in a series of which the first two were held in Skokloster, Sweden in 1970 and Boldern, Switzerland in 1974. The Proceedings of the meetings indicate a rapid development of knowledge of cholinergiC mechanisms which for many years lagged behind that of other neurotransmitters and neuroregulators. The inclusion of a large section in the present volume dealing with clinical manifestations of cholinergiC dysfunction reflects one of the most important trends in current research on cholinergiC mechanisms, namely the close inter-relationship and mutual support of basic science and clinical investigation. I hope that this volume will be of value to all those whose work relates to cholinergiC function, at both basic and clinicalleve18, and will continue to stimulate the vigorous exchange of ideas which was such a prominent feature of the Symposium.

Providing a cutting-edge profile of research progress in this important field of study, Cholinergic Mechanisms: Function and Dysfunction contains a compilation of the proceedings of the Eleventh ISCM, held in St. Moritz, May 2002. Bringing together 250 contributors from 30 countries, the book presents a comprehensive picture of the cholinergic field. It provides a survey of current understanding of molecular, pharmacological, toxicological, behavioral, and clinical aspects of the cholinergic system. This volume offers a state-of-the-art account of progress in the field from the molecule in the test tube through the cell and the synapse, to the organism and the patient.

Every three years early Spring witnesses the convening of a small group of neuroscientists from many parts of the world. They are devoted to the study of acetylcholine, the oldest of the known neurotransmitters. To assess the level of knowledge, to take stock of the still unsolved problems, to evaluate the practical meaning of their findings, the cholinologists first met in 1969 in the eerie atmosphere of a snow-covered Swedish forest, the second in the Swiss Alps, the third facing the surf and foam of the Paci fic waves. Finally in March 1980 Florence, her trees burgeoning in the mild rain of March, confronted them with the temptation of her monuments and museums. But the cholinologists bravely dismis sed the temptations and went on with the presentations and discus sions of the many papers which form the present book. The papers describe the most recent development of investiga tions on acetylcholine. They open with an extensive coverage of the developmental and phylogenetic aspects of the cholinergic neurons. The regulation of acetylcholine synthesis, release, post synaptic, electrical and trophic effects in the peripheral chol inergic synapses including ganglia, neuromuscular junction, myen theric plexus and heart is then covered. Special emphasis is given to the cholinergic mechanisms in the eye.

Presents a comprehensive update of central cholinergic mechanisms from their most molecular aspects to possible clinical applications modifying cholinergic neurotransmission. A considerable number of high-calibre scientists from several continents contributed to this volume.