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Author: Adam C. Errington Publisher: Springer ISBN: 149391426X Category : Medical Languages : en Pages : 301
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: Adam C. Errington Publisher: Springer ISBN: 149391426X Category : Medical Languages : en Pages : 301
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: Jeffrey Noebels Publisher: OUP USA ISBN: 0199746540 Category : Medical Languages : en Pages : 1258
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: Salvatore J. Enna Publisher: Humana Press ISBN: 9781588298133 Category : Medical Languages : en Pages : 325
Book Description
The Gaba Receptors, Third Edition, presents a critical appraisal of our current understanding of the molecular, behavioral, biochemical, clinical, and pharmacological properties of GABA receptors. Emphasis is placed on exploring cutting-edge findings on the structureal properties of receptor sites, mechanisms of receptor expression, chemical agents that differentiate receptor subtypes, and phenotypes displayed by GABA receptor null mice. Chapters in this updated and expanded edition examine such topics as GABA receptor subypes, trafficking postsynaptic GABA receptors, GABA receptor mutations associated with idiopathic generalized epilepsies and febrile seizures, and GABA receptors as a potential therapeutic target.
Author: Janko Samardzic Publisher: BoD – Books on Demand ISBN: 9535138219 Category : Medical Languages : en Pages : 139
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: Sean Booth Christie Publisher: ISBN: Category : Electronic dissertations Languages : en Pages :
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
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: Devin K. Binder Publisher: Springer Science & Business Media ISBN: 147576376X Category : Medical Languages : en Pages : 265
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: Jan Egebjerg Publisher: CRC Press ISBN: 9780748408818 Category : Science Languages : en Pages : 456
Book Description
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.
Author: Wucheng Tao Publisher: ISBN: Category : Languages : en Pages : 73
Book Description
Classically, GABAB receptors regulate neurotransmission primarily through presynaptic mechanisms that inhibit neurotransmitter release, and thus inhibit GABAA receptor function. Many studies have shown that postsynaptic GABAB receptors have no direct functional effects on GABAA receptors. In this thesis, I describe novel results that indicate postsynaptic GABAB receptors activation enhances GABAA receptor function in dentate gyrus granule cells (DGGCs). During my early experiments on DGGCs, I made the surprising observation that inhibition of GABAB receptors reduced the amplitude of currents mediated by GABAA receptors. Intrigued by this exciting and unexpected result, I shifted my research to address the following three questions: 1) Do GABAB receptors regulate GABAA receptor function? 2) What are the molecular mechanisms responsible for enhancement of GABAA currents following GABAB receptor activation? and 3) What are the signaling pathways involved in this modulation? Based on these questions, I divide my thesis contents into four chapters. Chapter 1 presents an introductory review of GABAA receptors and GABAB receptors and a summary of my thesis. The main parts of this thesis with descriptions of results addressing the three questions above are presented in chapter 2 - 4: In chapter 2, I found that in dentate gyrus granule cells, postsynaptic GABAB receptor activation enhanced extrasynaptic GABAA receptor function with no effect on synaptic GABAA receptors. Specially, this modulation was cell type specific and only occurs in cell type with delta subunit-containing GABAA receptors. Also, this modulation did not occur at resting condition and required increase of ambient GABA concentration; in chapter 3, I found GABAB receptor activation increased surface expression of delta subunit-containing GABAA receptors with no change in its total protein expression or single channel conductance or channel kinetics of GABAA receptors; in chapter 4, I found that GABAB receptor modulation of GABAA receptors required two signaling pathways, one was mediated by PKA and other one was PKC; and these two signaling pathways worked in opposite directions to modulate surface expression of delta subunit-containing GABAA receptors and GABA currents. As DGGCs act as a gate for hippocampus to prevent excessive excitation inputs from entorhinal cortex, the mechanisms (enhancement of tonic inhibition by membrane trafficking of delta subunit-containing GABAA receptors) I found here maybe utilized by DGGCs to enhance their gating role.
Author: Adam C. Errington
Author: Adam C. Errington
Author: Jeffrey Noebels
Author: Ce Zhang
Author: Salvatore J. Enna
Author: Janko Samardzic
Author: Sean Booth Christie
Author: Alain Destexhe
Author: Devin K. Binder
Author: Jan Egebjerg![GABA-B Receptors Regulate Extrasynaptic GABA-[subscript A] Receptors PDF](https://books.google.com/books/content/images/frontcover/ljNvrgEACAAJ?fife=w80-h100)
Author: Wucheng Tao