The molecular genetics of the cholinergic system including both muscarinic and nicotinic acetylcholine receptors, cholinesterases, acetylcholine synthesis and release have provided significant insights into potential targeting for pharmacological intervention. Cholinergic drugs are being used or evaluated for the treatment of diseases. Thus, this volume aims to broaden our understanding of the current state of cholinergic mechanisms to enable implementation of novel approaches for the development of more effective treatments.

Using the most well-studied behavioral analyses of animal subjects to promote a better understanding of the effects of disease and the effects of new therapeutic treatments on human cognition, Methods of Behavior Analysis in Neuroscience provides a reference manual for molecular and cellular research scientists in both academia and the pharmaceutic

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.

Basic Neurochemistry, Eighth Edition, is the updated version of the outstanding and comprehensive classic text on neurochemistry. For more than forty years, this text has been the worldwide standard for information on the biochemistry of the nervous system, serving as a resource for postgraduate trainees and teachers in neurology, psychiatry, and basic neuroscience, as well as for medical, graduate, and postgraduate students and instructors in the neurosciences. The text has evolved, as intended, with the science. This new edition continues to cover the basics of neurochemistry as in the earlier editions, along with expanded and additional coverage of new research from intracellular trafficking, stem cells, adult neurogenesis, regeneration, and lipid messengers. It contains expanded coverage of all major neurodegenerative and psychiatric disorders, including the neurochemistry of addiction, pain, and hearing and balance; the neurobiology of learning and memory; sleep; myelin structure, development, and disease; autism; and neuroimmunology. - Completely updated text with new authors and material, and many entirely new chapters - Over 400 fully revised figures in splendid color - 61 chapters covering the range of cellular, molecular and medical neuroscience - Translational science boxes emphasizing the connections between basic and clinical neuroscience - Companion website at http://elsevierdirect.com/companions/9780123749475

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.

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 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.

The physiological or psychological stresses that employees bring to their workplace affect not only their own performance but that of their co-workers and others. These stresses are often compounded by those of the job itself. Medical personnel, firefighters, police, and military personnel in combat settingsâ€"among othersâ€"experience highly unpredictable timing and types of stressors. This book reviews and comments on the performance-enhancing potential of specific food components. It reflects the views of military and non-military scientists from such fields as neuroscience, nutrition, physiology, various medical specialties, and performance psychology on the most up-to-date research available on physical and mental performance enhancement in stressful conditions. Although placed within the context of military tasks, the volume will have wide-reaching implications for individuals in any job setting.

Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.