Fast inhibitory transmission exerts a powerful control on neuronal excitability and network oscillations thought to be associated with high cognitive functions. An alteration of inhibitory signaling is associated with major neurological and psychiatric disorders including epilepsy. Once released from presynaptic nerve terminals, GABA and glycine cross the synaptic cleft and bind to postsynaptic receptors localized in precise apposition to presynaptic release sites. The functional organization of inhibitory synapses consists in a dynamic process which relies on a number of highly specialized proteins that ensure the correct targeting, clustering, stabilization and subsequent fate of synaptic receptors. Among the proteins involved in this task, the tubulin-binding protein gephyrin plays a crucial role. Through its self-oligomerization properties, this protein forms hexagonal lattices that trap GABAA and glycine receptors and link them to the cytoskeleton. By directly interacting with cell-adhesion molecules of the neuroligin-neurexin families that connect presynaptic and postsynaptic neurons at synapses, gephyrin ensures a backward control of presynaptic signaling. In addition, changes in clusters size is dynamically regulated by lateral diffusion of neurotransmitter receptors between the synaptic and extrasynaptic compartments and by their interaction with synaptic scaffold proteins. The aim of this Research Topic (research articles and reviews) is to bring together experts on the cellular and molecular mechanisms regulating the appropriate assembly, location and function of pre and postsynaptic specializations at inhibitory synapses. A particular emphasis will be on the role of receptor trafficking in synaptic stabilization and plasticity.

Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.

This volume will explore the most recent findings on cellular mechanisms of inhibitory plasticity and its functional role in shaping neuronal circuits, their rewiring in response to experience, drug addiction and in neuropathology. Inhibitory Synaptic Plasticity will be of particular interest to neuroscientists and neurophysiologists.

Brain aminergic pathways are organized in parallel and interacting systems, which support a range of functions, from homoeostatic regulations to cognitive, and motivational processes. Despite overlapping functional influences, dopamine, serotonin, noradrenaline and histamine systems provide different contributions to these processes. The histaminergic system, long ignored as a major regulator of the sleep-wake cycle, has now been fully acknowledged also as a major coordinator of attention, learning and memory, decision making. Although histaminergic neurons project widely to the whole brain, they are functionally heterogeneous, a feature which may provide the substrate for differential regulation, in a region-specific manner, of other neurotransmitter systems. Neurochemical preclinical studies have clearly shown that histamine interacts and modulates the release of neurotransmitters that are recognized as major modulators of cognitive processing and motivated behaviours. As a consequence, the histamine system has been proposed as a therapeutic target to treat sleep-wake disorders and cognitive dysfunctions that accompany neurodegenerative and neuroinflammatory pathologies. Last decades have witnessed an unexpected explosion of interest in brain histamine system, as new receptors have been discovered and selective ligands synthesised. Nevertheless, the complete picture of the histamine systems fine-tuning and its orchestration with other pathways remains rather elusive. This Research Topic is intended to offer an inter-disciplinary forum that will improve our current understanding of the role of brain histamine and provide the fundamentals necessary to drive innovation in clinical practice and to improve the management and treatment of neurological disorders.

This book has brought together leading investigators who work in the new arena of brain connectomics. This includes ‘macro-connectome’ efforts to comprehensively chart long-distance pathways and functional networks; ‘micro-connectome’ efforts to identify every neuron, axon, dendrite, synapse, and glial process within restricted brain regions; and ‘meso-connectome’ efforts to systematically map both local and long-distance connections using anatomical tracers. This book highlights cutting-edge methods that can accelerate progress in elucidating static ‘hard-wired’ circuits of the brain as well as dynamic interactions that are vital for brain function. The power of connectomic approaches in characterizing abnormal circuits in the many brain disorders that afflict humankind is considered. Experts in computational neuroscience and network theory provide perspectives needed for synthesizing across different scales in space and time. Altogether, this book provides an integrated view of the challenges and opportunities in deciphering brain circuits in health and disease.

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.

Neural network research often builds on the fiction that neurons are simple linear threshold units, completely neglecting the highly dynamic and complex nature of synapses, dendrites, and voltage-dependent ionic currents. Biophysics of Computation: Information Processing in Single Neurons challenges this notion, using richly detailed experimental and theoretical findings from cellular biophysics to explain the repertoire of computational functions available to single neurons. The author shows how individual nerve cells can multiply, integrate, or delay synaptic inputs and how information can be encoded in the voltage across the membrane, in the intracellular calcium concentration, or in the timing of individual spikes.Key topics covered include the linear cable equation; cable theory as applied to passive dendritic trees and dendritic spines; chemical and electrical synapses and how to treat them from a computational point of view; nonlinear interactions of synaptic input in passive and active dendritic trees; the Hodgkin-Huxley model of action potential generation and propagation; phase space analysis; linking stochastic ionic channels to membrane-dependent currents; calcium and potassium currents and their role in information processing; the role of diffusion, buffering and binding of calcium, and other messenger systems in information processing and storage; short- and long-term models of synaptic plasticity; simplified models of single cells; stochastic aspects of neuronal firing; the nature of the neuronal code; and unconventional models of sub-cellular computation.Biophysics of Computation: Information Processing in Single Neurons serves as an ideal text for advanced undergraduate and graduate courses in cellular biophysics, computational neuroscience, and neural networks, and will appeal to students and professionals in neuroscience, electrical and computer engineering, and physics.