Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.

Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction.

An illuminating summary of our current understanding of the interactive role of dopamine and glutamate in psychiatric diseases and the therapeutic strategies and possibilities for future treatment. Among the new ideas presented are hypotheses on the role of dopamine and glutamate in aggression, the glutamate system in anxiety disorders, glutamate and neurodegeneration, and on the origin and progression of Parkinson's disease. Additional chapters offer novel insights into a variety of psychiatric diseases, including ADHD, stress, aggression, addiction, schizophrenia, depression, social phobias, dementias, bulimia, and neurodegenerative diseases like Parkinson's and Alzheimer's diseases. Each chapter summarizes the prevalence and symptoms of the disease and explains the involvement of dopamine and/or glutamate systems using the newer molecular approaches such as transgenic knockout or knockin mice and recent brain imaging techniques.

The volume presents a comprehensive and up-to-date treatise of the glutamatergic synapse and its environment. Particular emphasis is on the localizations of the molecular constituents of the synaptic machinery. Immunogold and other high-resolution methods are used extensively. Each chapter presents new data that have not previously been reviewed. The material presented forms the basis for work directed to understanding the functional properties of excitatory synapses in greater depth, to discover mechanisms of neurological and psychiatric disorders and novel methods for treatment. Chapter 1 deals with the transmitter molecule itself, mechanisms of release and pathways for glutamate synthesis. The anatomy of glutamatergic nerve projection pathways in different brain regions is dealt with. In Chapter 2, focus is on aspartate, the enigmatic congener of glutamate, and its possible role in excitatory neurotransmission. Chapters 3 through 6 deal with glutamate receptors. Metabotropic glutamate receptors are presented in Chapter 3. Chapter 4 presents an in situ hybridization atlas of the different classes of ionotropic glutamate receptors. The localizations of these receptors at the regional and synaptic level are presented in Chapter 5. The ways in which the receptors are brought to the synapse and held in position are the subject of Chapter 6. Chapter 7 deals with the enzymes responsible for formation and catabolism of glutamate. In Chapter 8, the regulation of extracellular glutamate levels by glutamate transporters is discussed. The final two chapters of the volume focus on two "model synapses" that, due to special features, lend themselves particularly well to demonstrating properties of glutamatergic synapses. The hair cell-to-afferent nerve terminal synapses in the inner ear (Chapter 9), with their supporting cells, share essential properties with glutamatergic synapses in the central nervous system. The salient features of the latter are illustrated by the synapses of the giant reticulo-spinal axons of the lamprey, used to unravel molecular mechanisms of the cycling of synaptic vesicles (Chapter 10).

The ubiquitous presence of glutamate and GABA receptors in the nervous system makes these receptor systems pivotal to our understanding of neurotransmission. Cloning of the molecular components of these receptor systems has provided insights to the selectivity of many drugs and detailed characterisation at the molecular level is emerging. Moreover, continuous development of novel and selective drugs has revealed detailed information on the mechanism of receptor activation and regulation. However, the rapid development of different aspects of glutamate and GABA receptor research makes it increasingly difficult to establish a general view of the field. Studies of the receptors are a multi-disciplinary task employing many specialised techniques. This book conveys recent discoveries in a framework of the basic concepts in the field of glutamate and GABA receptor research. Glutamate and GABA Receptors and Transporters: Structure, Function and Pharmacology is suitable for postgraduate students studying ligand gated channels but also beneficial for industrial and academic research scientists in both the glutamate and GABA field. Universities offering programs in neuroscience, molecular pharmacology or medicinal chemistry will find this a valuable reference.

This book collates the contributions of a selected number of neuroscientists that are interested in the molecular, preclinical, and clinical aspects of neurotransmission research. The seven chapters in this book address the latest research/review data related to GABA/glutamate system's organization and function, the structure of receptors, subtypes and their ligands, as well as the translational approach and clinical implications. The book offers readers a rich collection of data regarding current and future applications of GABA and glutamate neurotransmission, including promising research strategies and potential clinical benefits.