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Excitatory glutamate receptors

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https://www.readbyqxmd.com/read/28811138/intermittent-hypoxia-training-powerful-non-invasive-cerebroprotection-against-ethanol-withdrawal-excitotoxicity
#1
REVIEW
Marianna E Jung, Robert T Mallet
Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca(2+) loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence...
August 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28807676/crf-modulates-glutamate-transmission-in-the-central-amygdala-of-na%C3%A3-ve-and-ethanol-dependent-rats
#2
Florence P Varodayan, Diego Correia, Dean Kirson, Sophia Khom, Christopher S Oleata, George Luu, Paul Schweitzer, Marisa Roberto
Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) is hypothesized to drive the development of alcohol dependence, as it regulates ethanol intake and several anxiogenic behaviors linked to withdrawal. Excitatory glutamatergic neurotransmission contributes to alcohol reinforcement, tolerance and dependence. Therefore, in this study we used in vitro slice electrophysiology to investigate the effects of CRF and its receptor subtype (CRF1 and CRF2) antagonists on both evoked and spontaneous action potential-independent glutamatergic transmission in the CeA of naive and ethanol-dependent Sprague-Dawley rats...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28794459/multiple-excitatory-actions-of-orexins-upon-thalamo-cortical-neurons-in-dorsal-lateral-geniculate-nucleus-implications-for-vision-modulation-by-arousal
#3
Lukasz Chrobok, Katarzyna Palus-Chramiec, Anna Chrzanowska, Mariusz Kepczynski, Marian Henryk Lewandowski
The orexinergic system of the lateral hypothalamus plays a crucial role in maintaining wakefulness and mediating arousal in a circadian time-dependent manner. Due to the extensive connections of orexinergic neurons, both orexins (OXA and OXB) exert mainly excitatory effects upon remote brain areas, including the thalamus. The dorsal lateral geniculate nucleus (DLG) is a relay thalamic centre for the visual system. Its thalamo-cortical (TC) neurons convey photic information from the retina to the primary visual cortex...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782641/nitric-oxide-cgmp-signaling-via-guanylyl-cyclase-isoform-1-modulates-glutamate-and-gaba-release-in-somatosensory-cortex-of-mice
#4
Qi Wang, Evanthia Mergia, Doris Koesling, Thomas Mittmann
In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input-output curves of evoked signals, which indicated the reduction of glutamate and GABA release in NO-GC1 KO mice...
August 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28780133/altered-glua1-gria1-function-and-accumbal-synaptic-plasticity-in-the-clock%C3%AE-19-model-of-bipolar-mania
#5
Puja K Parekh, Darius Becker-Krail, Poornima Sundaravelu, Shinsuke Ishigaki, Haruo Okado, Gen Sobue, Yanhua Huang, Colleen A McClung
BACKGROUND: Disruptions in circadian rhythms are associated with an increased risk for bipolar disorder. Moreover, studies show that the circadian protein CLOCK (circadian locomotor output cycles kaput) is involved in regulating monoaminergic systems and mood-related behavior. However, the molecular and synaptic mechanisms underlying this relationship remain poorly understood. METHODS: Using ex vivo whole-cell patch-clamp electrophysiology in ClockΔ19 mutant and wild-type mice we characterized alterations in excitatory synaptic transmission, strength, and intrinsic excitability of nucleus accumbens (NAc) neurons...
June 27, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28776199/contribution-of-vesicular-glutamate-transporters-to-stress-response-and-related-psychopathologies-studies-in-vglut3-knockout-mice
#6
REVIEW
Hanga Réka Horváth, Csilla Lea Fazekas, Diána Balázsfi, Subodh Kumar Jain, József Haller, Dóra Zelena
Maintenance of the homeostasis in a constantly changing environment is a fundamental process of life. Disturbances of the homeostatic balance is defined as stress response and is induced by wide variety of challenges called stressors. Being the main excitatory neurotransmitter of the central nervous system glutamate is important in the adaptation process of stress regulating both the catecholaminergic system and the hypothalamic-pituitary-adrenocortical axis. Data are accumulating about the role of different glutamatergic receptors at all levels of these axes, but little is known about the contribution of different vesicular glutamate transporters (VGluT1-3) characterizing the glutamatergic neurons...
August 3, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28768996/functional-expression-of-organic-ion-transporters-in-astrocytes-and-their-potential-as-a-drug-target-in-the-treatment-of-central-nervous-system-diseases
#7
Tomomi Furihata, Naohiko Anzai
It has become widely acknowledged that astrocytes play essential roles in maintaining physiological central nervous system (CNS) activities. Astrocytes fulfill their roles partly through the manipulation of their plasma membrane transporter functions, and therefore these transporters have been regarded as promising drug targets for various CNS diseases. A representative example is excitatory amino acid transporter 2 (EAAT2), which works as a critical regulator of excitatory signal transduction through its glutamate uptake activity at the tripartite synapse...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28768770/nmda-receptors-mediate-leptin-signaling-and-regulate-potassium-channel-trafficking-in-pancreatic-%C3%AE-cells
#8
Yi Wu, Dale A Fortin, Veronica A Cochrane, Pei-Chun Chen, Show-Ling Shyng
NMDA receptors (NMDARs) are Ca2+-permeant, ligand-gated ion channels activated by the excitatory neurotransmitter glutamate and have well-characterized roles in the nervous system. The expression and function of NMDARs in pancreatic β cells, by contrast, are poorly understood. Here, we report a novel function of NMDARs in β-cells. Using a combination of biochemistry, electrophysiology, and imaging techniques we now show that NMDARs have a key role in mediating the effect of leptin to modulate β-cell electrical activity by promoting AMP-activated protein kinase (AMPK)-dependent trafficking of KATP and Kv2...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768197/dual-effects-of-tarp-%C3%AE-2-on-glutamate-efficacy-can-account-for-ampa-receptor-autoinactivation
#9
Ian D Coombs, David M MacLean, Vasanthi Jayaraman, Mark Farrant, Stuart G Cull-Candy
Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs) associated with transmembrane AMPAR regulatory proteins (TARPs). At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28768196/a-cooperative-mechanism-involving-ca-2-permeable-ampa-receptors-and-retrograde-activation-of-gabab-receptors-in-interpeduncular-nucleus-plasticity
#10
Peter Koppensteiner, Riccardo Melani, Ipe Ninan
The medial habenula-interpeduncular nucleus (MHb-IPN) pathway, which connects the limbic forebrain to the midbrain, has recently been implicated in aversive behaviors. The MHb-IPN circuit is characterized by a unique topographical organization, an excitatory role of GABA, and a prominent co-release of neurotransmitters and neuropeptides. However, little is known about synaptic plasticity in this pathway. An application of a high-frequency stimulation resulted in a long-lasting potentiation of glutamate release in IPN neurons...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28762946/plasticity-of-calcium-permeable-ampa-glutamate-receptors-in-pro-opiomelanocortin-neurons
#11
Shigetomo Suyama, Alexandra Ralevski, Zhong-Wu Liu, Marcelo O Dietrich, Toshihiko Yada, Stephanie E Simonds, Michael A Cowley, Xiao-Bing Gao, Sabrina Diano, Tamas L Horvath
POMC neurons integrate metabolic signals from the periphery. Here, we show in mice that food deprivation induces a linear current-voltage relationship of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2 subunits into the AMPA receptor complex during food deprivation. Accordingly, removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in the fed but not the fasted state...
August 1, 2017: ELife
https://www.readbyqxmd.com/read/28762944/synaptic-plasticity-through-activation-of-glua3-containing-ampa-receptors
#12
Maria C Renner, Eva Hh Albers, Nicolas Gutierrez-Castellanos, Niels R Reinders, Aile N van Huijstee, Hui Xiong, Tessa R Lodder, Helmut W Kessels
Excitatory synaptic transmission is mediated by AMPA-type glutamate receptors (AMPARs). In CA1 pyramidal neurons of the hippocampus two types of AMPARs predominate: those that contain subunits GluA1 and GluA2 (GluA1/2), and those that contain GluA2 and GluA3 (GluA2/3). Whereas subunits GluA1 and GluA2 have been extensively studied, the contribution of GluA3 to synapse physiology has remained unclear. Here we show in mice that GluA2/3s are in a low-conductance state under basal conditions, and although present at synapses they contribute little to synaptic currents...
August 1, 2017: ELife
https://www.readbyqxmd.com/read/28760974/structural-basis-of-subunit-selectivity-for-competitive-nmda-receptor-antagonists-with-preference-for-glun2a-over-glun2b-subunits
#13
Genevieve E Lind, Tung-Chung Mou, Lucia Tamborini, Martin G Pomper, Carlo De Micheli, Paola Conti, Andrea Pinto, Kasper B Hansen
NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (GluN2A-D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists, of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we show has 11-fold preference for GluN1/2A over GluN1/2B...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28757327/differential-electrophysiological-and-morphological-alterations-of-thalamostriatal-and-corticostriatal-projections-in-the-r6-2-mouse-model-of-huntington-s-disease
#14
Anna Parievsky, Cindy Moore, Talia Kamdjou, Carlos Cepeda, Charles K Meshul, Michael S Levine
Huntington's disease (HD) is a fatal genetic disorder characterized by cell death of medium-sized spiny neurons (MSNs) in the striatum, traditionally attributed to excessive glutamate inputs and/or receptor sensitivity. While changes in corticostriatal projections have typically been studied in mouse models of HD, morphological and functional alterations in thalamostriatal projections have received less attention. In this study, an adeno-associated virus expressing channelrhodopsin-2 under the calcium/calmodulin-dependent protein kinase IIα promoter was injected into the sensorimotor cortex or the thalamic centromedian-parafascicular nuclear complex in the R6/2 mouse model of HD, to permit selective activation of corticostriatal or thalamostriatal projections, respectively...
July 27, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28754924/dynamic-scaffolds-for-neuronal-signaling-in-silico-analysis-of-the-tanc-protein-family
#15
Alessandra Gasparini, Silvio C E Tosatto, Alessandra Murgia, Emanuela Leonardi
The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins have been reported as postsynaptic scaffolds influencing synaptic spines and excitatory synapse strength, their molecular functions remain unknown. Here, we conducted a comprehensive in silico analysis of the TANC protein family to characterize their molecular role and understand possible neurobiological consequences of their disruption...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747405/nmda-receptor-dependent-presynaptic-inhibition-at-the-calyx-of-held-synapse-of-rat-pups
#16
Tomoko Oshima-Takago, Hideki Takago
N-Methyl-d-aspartate receptors (NMDARs) play diverse roles in synaptic transmission, synaptic plasticity, neuronal development and neurological diseases. In addition to their postsynaptic expression, NMDARs are also expressed in presynaptic terminals at some central synapses, and their activation modulates transmitter release. However, the regulatory mechanisms of NMDAR-dependent synaptic transmission remain largely unknown. In the present study, we demonstrated that activation of NMDARs in a nerve terminal at a central glutamatergic synapse inhibits presynaptic Ca(2+) currents (ICa) in a GluN2C/2D subunit-dependent manner, thereby decreasing nerve-evoked excitatory postsynaptic currents...
July 2017: Open Biology
https://www.readbyqxmd.com/read/28744210/transition-dynamics-of-a-dentate-gyrus-ca3-neuronal-network-during-temporal-lobe-epilepsy
#17
Liyuan Zhang, Denggui Fan, Qingyun Wang
In temporal lobe epilepsy (TLE), the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin-Huxley (HH) type neurons and Pinsky-Rinzel (PR) type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG) region and CA3 region...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28738332/neuroprogression-and-immune-activation-in-major-depressive-disorder
#18
Jeffrey H Meyer
Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28737760/channel-opening-and-gating-mechanism-in-ampa-subtype-glutamate-receptors
#19
Edward C Twomey, Maria V Yelshanskaya, Robert A Grassucci, Joachim Frank, Alexander I Sobolevsky
AMPA-subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the central nervous system. Gated by the neurotransmitter glutamate, AMPA receptors are critical for synaptic strength and dysregulation of AMPA receptor-mediated signalling is linked to numerous neurological diseases. Here, we use cryo-electron microscopy to solve the structures of AMPA receptor-auxiliary subunit complexes in the apo, antagonist and agonist-bound states and elucidate the iris-like mechanism of ion channel opening...
July 24, 2017: Nature
https://www.readbyqxmd.com/read/28734063/atp-and-astrocytes-play-a-prominent-role-in-the-control-of-the-respiratory-pattern-generator-in-the-lamprey
#20
Elenia Cinelli, Ludovica Iovino, Donatella Mutolo
The role of ATP and astrocytes in respiratory rhythm modulation has been recently investigated in neonatal rodents. However, no information on the role of ATP and astrocytes within the respiratory network of the lamprey is available, particularly within the paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator. To address these issues, the present study was carried out on isolated brainstems of the adult lamprey. Bath application of ATP caused marked increases in respiratory frequency followed by decreases in the respiratory motor output, mediated by the ATP metabolite adenosine at the level of the pTRG...
July 22, 2017: Journal of Physiology
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