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.

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.

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 book provides the reader with background information on neurotransmitter release. Emphasis is placed on the rationale by which proteins are assigned specific functions rather than just providing facts about function.

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.

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.

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed “tonic” inhibition, has been described. Whereas synaptic GABAA receptors underlie classical “phasic” GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.