The Role of Extrasynaptic GABAA Receptors in Regulation of Inhibitory Synapses PDF Download

Author: Adam C. Errington
Publisher: Springer
ISBN: 149391426X
Category : Medical
Languages : en
Pages : 301

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Book Description
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.

Author: Ce Zhang
Publisher:
ISBN:
Category :
Languages : en
Pages : 30

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Book Description

Author: Jeffrey Noebels
Publisher: OUP USA
ISBN: 0199746540
Category : Medical
Languages : en
Pages : 1258

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Book Description
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.

Author: Enrico Cherubini
Publisher: Frontiers E-books
ISBN: 2889190978
Category :
Languages : en
Pages : 159

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Book Description
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.

Author: Andrea Barberis
Publisher: Frontiers Media SA
ISBN: 2889197328
Category : Learning
Languages : en
Pages : 177

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Book Description
Learning and memory are believed to depend on plastic changes of neuronal circuits due to activity-dependent potentiation or depression of specific synapses. During the last two decades, plasticity of brain circuits was hypothesized to mainly rely on the flexibility of glutamatergic excitatory synapses, whereas inhibitory synapses were assumed relatively invariant, to ensure stable and reliable control of the neuronal network. As a consequence, while considerable efforts were made to clarify the main mechanisms underlying plasticity at excitatory synapses, the study of the cellular/molecular mechanisms of inhibitory plasticity has received much less attention. Nevertheless, an increasing body of evidence has revealed that inhibitory synapses undergo several types of plasticity at both pre- and postsynaptic levels. Given the crucial role of inhibitory interneurons in shaping network activities, such as generation of oscillations, selection of cell assemblies and signal integration, modifications of the inhibitory synaptic strength represents an extraordinary source of versatility for the fine control of brain states. This versatility also results from the rich diversity of GABAergic neurons in several brain areas, the specific role played by each inhibitory neuron subtype within a given circuit, and the heterogeneity of the properties and modulation of GABAergic synapses formed by specific interneuron classes. The molecular mechanisms underlying the potentiation or depression of inhibitory synapses are now beginning to be unraveled. At the presynaptic level, retrograde synaptic signaling was demonstrated to modulate GABA release, whereas postsynaptic forms of plasticity involve changes in the number/gating properties of GABAA receptors and/or shifts of chloride gradients. In addition, recent research indicates that GABAergic tonic inhibition can also be plastic, adding a further level of complexity to the control of the excitatory/inhibitory balance in the brain. The present Topic will focus on plasticity of GABAergic synapses, with special emphasis on the molecular mechanisms of plasticity induction and/or expression.

Author: Devin K. Binder
Publisher: Springer Science & Business Media
ISBN: 147576376X
Category : Medical
Languages : en
Pages : 265

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Book Description
Epilepsy research has entered an exciting phase as advances in molecular analysis have supplemented in vitro and in vivo electrophysiologic and phenotypic characterization. Recent Advances in Epilepsy Research sets forth a series of chapter reviews by researchers involved in these advances. This volume is a composite profile of some exciting recent investigations in select areas of enquiry. Key features: neurogenetics of seizure disorders, new developments in cellular and molecular neurobiology of seizure disorders, the role of growth factors in seizures, new advances in the roles of metabotropic glutamate receptors and GABA receptors and transporters, gap junctions, neuroimmunology of epilepsy, malformations of cortical development, neurogenesis, new animal models of epilepsy and the use of brain stimulation to treat epilepsy. This book should be of interest to a wide variety of audiences, including graduate students in neurobiology and related disciplines, neuroscientists, medical students, neurologists, neurosurgeons, and industry including pharmaceutical companies and medical device companies. There are many ideas in this book that will lead ingenious innovators in academia and industry to develop new and better therapies.

Author: Sean Booth Christie
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages :

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Book Description
Fast ionotropic inhibitory neurotransmission, mediated by presynaptic GABAergic terminals and correctly positioned postsynaptic GABAA receptors (GABAARs), occurs in about 30–40% of all synapses in the CNS. However, little is known about the specific control mechanisms responsible for patterned expression, assembly, trafficking, and targeting of GABAA receptors to GABAergic synapses or extrasynaptic domains within a single neuron. In this study, a cultured hippocampal neuron (CHN) model was used to examine the distribution and patterning of 13 different GABAAR subunit isoforms from 4 distinct subunit classes normally expressed in the brain. The group of experiments in this thesis shows that CHNs, as in the intact hippocampus, express and postsynaptically concentrate (cluster) GABA AR subtypes containing the α1–3, α 5, Î21–3, Î32S, Î32L and Î3 3 subunit isoforms. This postsynaptic clustering of GABAARs in CHNs primarily occurs apposed to inhibitory presynaptic contact and contains receptors with the Î32 or Î33 subunit. However, when presynaptic GABAergic terminals are absent from the local dendritic environment, significant GABAAR clustering occurs apposed to excitatory synaptic contact forming â€mismatched’ synapses. GABAAR clustering is particularly pronounced within the synapses onto the axon initial segment (AIS) of pyramidal cells in the brain, a phenomenon that also occurs in the AIS of CHNs independently of GABAergic or glutamatergic terminal phenotype. However, the coexistence of two different terminal phenotypes does not seem possible within this subcellular structure, due to the hierarchy of organizational signals created by correctly matched GABAergic synapses vs. mismatched synapses. Thus, we show that competition between GABAergic and glutamatergic terminals ultimately determines the postsynaptic localization of the GABAAR subtypes with a capacity for clustering. Lastly, this work addressed a molecular mechanism of GABAAR clustering. CHNs, as in the brain, are capable of expressing non-clustered GABAAR subtypes containing the Î ́ subunit. We have examined expression of chimeric subunits in which the large intracellular loops (IL) of Î32S and Î ́ subunits were exchanged. We show that while the Î32 IL is both necessary and central to the clustering process, it is not sufficient for clustering when incorporated into the Î ́ subunit. Thus, there are additional requirements other than the Î32-IL for receptor clustering that are as yet unidentified.

Author: Alain Destexhe
Publisher: Springer Science & Business Media
ISBN: 0387892796
Category : Medical
Languages : en
Pages : 428

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Book Description
Dynamic-clamp is a fascinating electrophysiology technique that consists of merging living neurons with computational models. The dynamic-clamp (also called “conductance injection”) allows experimentalists and theoreticians to challenge neurons (or any other type of cell) with complex conductance stimuli generated by a computer. The technique can be implemented from neural simulation environments and a variety of custom-made or commercial systems. The real-time interaction between the computer and cell also enables the design of recording paradigms with unprecedented accuracy via a computational model of the electrode. Dynamic-Clamp: From Principles to Applications contains contributions from leading researchers in the field, who investigate these paradigms at the cellular or network level, in vivo and in vitro, and in different brain regions and cardiac cells. Topics discussed include the addition of artificially-generated synaptic activity to neurons; adding, amplifying or neutralizing voltage-dependent conductances; creating hybrid networks with real and artificial cells; attaching simulated dendritic tree structures to the living cell; and connecting different neurons. This book will be of interest to experimental biophysicists, neurophysiologists, and cardiac physiologists, as well as theoreticians, engineers, and computational neuroscientists. Graduate and undergraduate students will also find up-to-date coverage of physiological problems and how they are investigated.

Author: Janko Samardzic
Publisher: BoD – Books on Demand
ISBN: 9535138219
Category : Medical
Languages : en
Pages : 139

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Book Description
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.

Author: Mark G. Darlison
Publisher: Springer
ISBN: 9783642091629
Category : Science
Languages : en
Pages : 0

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Book Description
Darlison’s excellent work reviews aspects of GABA-A receptor function, as well as the properties of a variety of other important inhibitory proteins, such as GABA-C receptors and G-protein coupled receptors including neuropeptides. Glycine receptors and potassium channels are covered too. The consequences of mutations that disrupt the regulation of excitatory neurotransmission, and efforts to target the GABAergic system for therapeutic benefit, are also discussed.