Author: Sean Booth ChristiePublisher:
ISBN:
Category :
Languages : en
Pages : 350
Book Description
Synaptic and Extrasynaptic GABA Receptors in Cultured Hippocampal Neurons
Author: Sean Booth ChristieSynaptic and Extrasynaptic Gabaa Receptors in Cultured Hippocampal Neurons
Author: Sean Booth ChristiePublisher:
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.
Extrasynaptic GABAA Receptors
Author: Adam C. ErringtonPublisher: 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.
Jasper's Basic Mechanisms of the Epilepsies
Author: Jeffrey NoebelsPublisher: 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.
Isolation of a Brain Fraction Enriched in GABAergic Type-II Postsynaptic Densities
Author: Xuejing LiBiology of the NMDA Receptor
Author: Antonius M. VanDongenPublisher: CRC Press
ISBN: 142004415X
Category : Medical
Languages : en
Pages : 368
Book Description
The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written
GABA And Glutamate
Author: Janko SamardzicPublisher: 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.
Differential Regulation of Synaptic and Extrasynaptic Α4 GABA(A) Receptor Populations by Protein Kinase A and Protein Kinase C in Cultured Cortical Neurons
Author: Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System
Author: Institute of MedicinePublisher: National Academies Press
ISBN: 0309212219
Category : Medical
Languages : en
Pages : 74
Book Description
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.
Cerebellar Cortex
Author: S.L. PalayPublisher: Springer Science & Business Media
ISBN: 3642655815
Category : Medical
Languages : en
Pages : 361
Book Description
The origins of this book go back to the first electron microscopic studies of the central nervous system. The cerebellar cortex was from the first an object of close study in the electron microscope, repeating in modern cytology and neuroanatomy the role it had in the hands of RAMON y CAJAL at the end of the nineteenth century. The senior author vividly remembers a day early in 1953 when GEORGE PALADE, with whom he was then working, showed him an electron micrograph of a cerebellar glomerulus, saying "That is what the synapse should look like. " It is true that the tissue was swollen and the mitochondria were exploded, but all of the essentials of synaptic structure were visible. At that time small fragments of tissue, fixed by immersion in osmium tetroxide and embedded in methacrylate, were laboriously sectioned with glass knives without any predetermined orientation and then examined in the electron microscope. After much searching, favorably preserved areas' were studied at the cytological level in order to recognize the parts of neurons and characterize them. Such procedures, dependent upon random sections and uncontrollable selection by a highly erratic technique of preservation, precluded any systematic investigation of the organization of a particular nucleus or region of the central nervous system. It was difficult enough to distinguish neurons from the neuroglia.