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Excitatory glutamate receptors

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https://www.readbyqxmd.com/read/28637049/protecting-oligodendrocytes-by-targeting-non-glutamate-receptors-as-a-new-therapeutic-strategy-for-ischemic-stroke
#1
Pan Luo, Dong Liu, Lianjun Guo
Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons...
June 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28636947/assembly-secretory-pathway-trafficking-and-surface-delivery-of-kainate-receptors-is-regulated-by-neuronal-activity
#2
Ashley J Evans, Sonam Gurung, Kevin A Wilkinson, David J Stephens, Jeremy M Henley
Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636915/probing-the-structural-dynamics-of-the-nmda-receptor-activation-by-coarse-grained-modeling
#3
Wenjun Zheng, Han Wen, Gary J Iacobucci, Gabriela K Popescu
N-Methyl-D-aspartate (NMDA) receptors are glutamate-gated excitatory channels that play essential roles in brain functions. High-resolution structures have been solved for an allosterically inhibited and agonist-bound form of a functional NMDA receptor; however, other key functional states (particularly the active open-channel state) were only resolved at moderate resolutions by cryo-electron microscopy (cryo-EM). To decrypt the mechanism of the NMDA receptor activation, structural modeling is essential to provide presently missing information about structural dynamics...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28628388/coordination-of-ampa-receptor-trafficking-by-rab-small-gtpases
#4
Angelika Hausser, Katalin Schlett
Synaptic connections in the brain are continuously weakened or strengthened in response to changes in neuronal activity. This process, known as synaptic plasticity, is the cellular basis for learning and memory, and is thought to be altered in several neuronal disorders. An important aspect of synaptic plasticity is the tightly controlled trafficking and synaptic targeting of the AMPA-type glutamate receptors, which are the major mediators of fast excitatory transmission in the brain. This review addresses the role of Rab GTPases in AMPA receptor trafficking in neurons under basal conditions and during activity-induced synaptic plasticity, especially during long-term potentiation (LTP) and long-term depression (LTD)...
June 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28621434/eea1-restores-homeostatic-synaptic-plasticity-in-hippocampal-neurons-from-rett-syndrome-mice
#5
Xin Xu, Lucas Pozzo-Miller
Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in MECP2, the gene encoding the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). Deletion of Mecp2 in mice results in an imbalance of synaptic excitation and inhibition in hippocampal pyramidal neurons, which affects "Hebbian" long-term synaptic plasticity. Since the excitatory/inhibitory (E/I) balance is maintained by homeostatic mechanisms, we examined the role of MeCP2 in homeostatic synaptic plasticity (HSP) at excitatory synapses...
June 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28617431/nicotine-protects-rat-hypoglossal-motoneurons-from-excitotoxic-death-via-downregulation-of-connexin-36
#6
Silvia Corsini, Maria Tortora, Rossana Rauti, Andrea Nistri
Motoneuron disease including amyotrophic lateral sclerosis may be due, at an early stage, to deficit in the extracellular clearance of the excitatory transmitter glutamate. A model of glutamate-mediated excitotoxic cell death based on pharmacological inhibition of its uptake was used to investigate how activation of neuronal nicotinic receptors by nicotine may protect motoneurons. Hypoglossal motoneurons (HMs) in neonatal rat brainstem slices were exposed to the glutamate uptake blocker DL-threo-β-benzyloxyaspartate (TBOA) that evoked large Ca(2+) transients time locked among nearby HMs, whose number fell by about 30% 4 h later...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28606116/characterization-of-serotonin-induced-inhibition-of-excitatory-synaptic-transmission-in-the-anterior-cingulate-cortex
#7
Zhen Tian, Manabu Yamanaka, Matteo Bernabucci, Ming-Gao Zhao, Min Zhuo
Excitatory synaptic transmission in central synapses is modulated by serotonin (5-HT). The anterior cingulate cortex (ACC) is an important cortical region for pain perception and emotion. ACC neurons receive innervation of projecting serotonergic nerve terminals from raphe nuclei, but the possible effect of 5-HT on excitatory transmission in the ACC has not been investigated. In the present study, we investigated the role of 5-HT on glutamate neurotransmission in the ACC slices of adult mice. Bath application of 5-HT produced dose-dependent inhibition of evoked excitatory postsynaptic currents (eEPSCs)...
June 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28605494/glutamate-transport-a-new-bench-to-bedside-mechanism-for-treating-drug-abuse
#8
Sade Spencer, Peter W Kalivas
Drug addiction has often been described as a "hijacking" of the brain circuits involved in learning and memory. Glutamate is the principal excitatory neurotransmitter in the brain, and its contribution to synaptic plasticity and learning processes is well established in animal models. Likewise, over the past twenty years the addiction field has ascribed a critical role for glutamatergic transmission in the development of addiction. Chronic drug use produces enduring neuroadaptations in corticostriatal projections that are believed to contribute to a maladaptive deficit in inhibitory control over behavior...
June 12, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28604219/potentiation-of-nmda-receptor-mediated-synaptic-transmission-at-the-parabrachial-central-amygdala-synapses-by-cgrp-in-mice
#9
Yuya Okutsu, Yukari Takahashi, Masashi Nagase, Kei Shinohara, Ryo Ikeda, Fusao Kato
The capsular part of the central amygdala (CeC) is called the "nociceptive amygdala," as it receives nociceptive information from various pathways, including monosynaptic input from the lateral part of the parabrachial nucleus (LPB), a major target of ascending neurons in the spinal and medullary dorsal horn. LPB-CeC synaptic transmission is mediated by glutamate but the fibers from the LPB also contain calcitonin gene-related peptide (CGRP) and the CeC is rich in CGRP-binding sites. CGRP might be released in response to strong nociception and activate these CGRP receptors...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28592819/spatial-and-temporal-boundaries-of-nmda-receptor-hypofunction-leading-to-schizophrenia
#10
Kazu Nakazawa, Vivek Jeevakumar, Kazuhito Nakao
The N-methyl-D-aspartate receptor hypofunction is one of the most prevalent models of schizophrenia. For example, healthy subjects treated with uncompetitive N-methyl-D-aspartate receptor antagonists elicit positive, negative, and cognitive-like symptoms of schizophrenia. Patients with anti-N-methyl-D-aspartate receptor encephalitis, which is likely caused by autoantibody-mediated down-regulation of cell surface N-methyl-D-aspartate receptors, often experience psychiatric symptoms similar to schizophrenia initially...
February 3, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28588066/identification-of-aicp-as-a-glun2c-selective-nmda-receptor-superagonist-at-the-glun1-glycine-site
#11
Maja Jessen, Kristen Frederiksen, Feng Yi, Rasmus P Clausen, Kasper B Hansen, Hans Brauner-Osborne, Paul Kilburn, Anders Damholt
NMDA-type ionotropic glutamate receptors mediate excitatory neurotransmission in the central nervous system and are critically involved in brain function. NMDA receptors are also implicated in psychiatric and neurological disorders and have received considerable attention as therapeutic targets. In this regard, administration of D-cycloserine (DCS), which is a glycine site NMDA receptor agonist, can enhance extinction of conditioned fear responses. The intriguing behavioral effects of DCS have been linked to its unique pharmacological profile among NMDA receptor subtypes (GluN1/2A-D), in which DCS is a superagonist at GluN2C-containing receptors compared to glycine and a partial agonist at GluN2B-containing receptors...
June 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28582391/all-atom-nmda-receptor-transmembrane-domain-model-development-and-simulations-in-lipid-bilayers-and-water
#12
Samaneh Mesbahi-Vasey, Lea Veras, Michael Yonkunas, Jon W Johnson, Maria G Kurnikova
N-methyl-d-aspartate receptors (NMDARs) are members of the ionotropic glutamate receptor family that mediate excitatory synaptic transmission in the central nervous system. The channels of NMDARs are permeable to Ca2+ but blocked by Mg2+, distinctive properties that underlie essential brain processes such as induction of synaptic plasticity. However, due to limited structural information about the NMDAR transmembrane ion channel forming domain, the mechanism of divalent cation permeation and block is understood poorly...
2017: PloS One
https://www.readbyqxmd.com/read/28580416/glua2-lacking-ampa-receptors-and-nitric-oxide-signaling-gate-spike-timing-dependent-potentiation-of-glutamate-synapses-in-the-dorsal-raphe-nucleus
#13
Samir Haj-Dahmane, Jean Claude Béïque, Roh-Yu Shen
The dorsal raphe nucleus (DRn) receives glutamatergic inputs from numerous brain areas that control the function of DRn serotonin (5-HT) neurons. By integrating these synaptic inputs, 5-HT neurons modulate a plethora of behaviors and physiological functions. However, it remains unknown whether the excitatory inputs onto DRn 5-HT neurons can undergo activity-dependent change of strength, as well as the mechanisms that control their plasticity. Here, we describe a novel form of spike-timing-dependent long-term potentiation (tLTP) of glutamate synapses onto rat DRn 5-HT neurons...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28575187/high-frequency-firing-activity-of-gnrh1-neurons-in-female-medaka-induces-the-release-of-gnrh1-peptide-from-their-nerve-terminals-in-the-pituitary
#14
Masaharu Hasebe, Yoshitaka Oka
Hypothalamic gonadotropin-releasing hormone (GnRH) neurons play an important role in promoting secretion of pituitary luteinizing hormone (LH) and ovulation by releasing GnRH peptide. The release of GnRH peptide is generally assumed to be mainly modulated according to the firing activity of GnRH neurons. However, the relationship between the firing activity and the release of GnRH peptide has been elusive. Here, we analyzed it by using two lines of transgenic medaka (gnrh1: EGFP and lhb: inverse-pericam) for the combined electrophysiological and Ca2+ imaging analyses...
May 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28565998/gabab-receptors-mediated-tonic-inhibition-of-glutamate-release-from-a%C3%AE-fibers-in-rat-laminae-iii-iv-of-the-spinal-cord-dorsal-horn
#15
Chiara Salio, Adalberto Merighi, Rita Bardoni
Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on Aβ fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28560253/spatial-and-temporal-boundaries-of-nmda-receptor-hypofunction-leading-to-schizophrenia
#16
Kazu Nakazawa, Vivek Jeevakumar, Kazuhito Nakao
The N-methyl-d-aspartate receptor hypofunction is one of the most prevalent models of schizophrenia. For example, healthy subjects treated with uncompetitive N-methyl-d-aspartate receptor antagonists elicit positive, negative, and cognitive-like symptoms of schizophrenia. Patients with anti-N-methyl-d-aspartate receptor encephalitis, which is likely caused by autoantibody-mediated down-regulation of cell surface N-methyl-d-aspartate receptors, often experience psychiatric symptoms similar to schizophrenia initially...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28559374/tarp-%C3%AE-2-is-required-for-inflammation-associated-ampa-receptor-plasticity-within-lamina-ii-of-the-spinal-cord-dorsal-horn
#17
Steve J Sullivan, Mark Farrant, Stuart G Cull-Candy
In the brain, transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs) critically influence the distribution, gating, and pharmacology of AMPARs, but the contribution of these auxiliary subunits to AMPAR-mediated signaling in the spinal cord remains unclear. We found that the type I TARP γ-2 (stargazin) is present in lamina II of the superficial dorsal horn (SDH), an area involved in nociception. Consistent with the notion that γ-2 is associated with surface AMPARs, CNQX, a partial agonist at AMPARs associated with type I TARPs, evoked whole-cell currents in lamina II neurons, but such currents were severely attenuated in γ-2-lacking stargazer (stg/stg) mice...
May 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28553558/phosphorylation-of-group-i-metabotropic-glutamate-receptors-in-drug-addiction-and-translational-research
#18
Li-Min Mao, Qiang Wang
Protein phosphorylation is an important posttranslational modification of group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes) which are widely distributed throughout the mammalian brain. Several common protein kinases are involved in this type of modification, including protein kinase A, protein kinase C, and extracellular signal-regulated kinase. Through constitutive and activity-dependent phosphorylation of mGluR1/5 at specific residues, protein kinases regulate trafficking, subcellular/subsynaptic distribution, and function of modified receptors...
September 2016: J Transl Neurosci
https://www.readbyqxmd.com/read/28549853/molecular-fingerprinting-of-principal-neurons-in-the-rodent-hippocampus-a-neuroinformatics-approach
#19
D J Hamilton, C M White, C L Rees, D W Wheeler, G A Ascoli
Neurons are often classified by their morphological and molecular properties. The online knowledge base Hippocampome.org primarily defines neuron types from the rodent hippocampal formation based on their main neurotransmitter (glutamate or GABA) and the spatial distributions of their axons and dendrites. For each neuron type, this open-access resource reports any and all published information regarding the presence or absence of known molecular markers, including calcium-binding proteins, neuropeptides, receptors, channels, transcription factors, and other molecules of biomedical relevance...
April 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28545760/identification-of-synaptic-pattern-of-nmda-receptor-subunits-upon-direction-selective-retinal-ganglion-cells-in-developing-and-adult-mouse-retina
#20
Jun-Seok Lee, Hang-Gu Kim, Chang-Jin Jeon
Direction selectivity of the retina is a unique mechanism and critical function of eyes for surviving. Direction-selective retinal ganglion cells (DS RGCs) strongly respond to preferred directional stimuli, but rarely respond to the opposite or null directional stimuli. These DS RGCs are sensitive to glutamate, which is secreted from bipolar cells. Using immunocytochemistry, we studied with the distributions of N-methyl-d-aspartate (NMDA) receptor subunits on the dendrites of DS RGCs in the developing and adult mouse retina...
May 22, 2017: Acta Histochemica
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