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GluN3A

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https://www.readbyqxmd.com/read/27798131/cocaine-exposure-enhances-the-activity-of-ventral-tegmental-area-dopamine-neurons-via-calcium-impermeable-nmdars
#1
Meaghan Creed, Jennifer Kaufling, Giulia R Fois, Marion Jalabert, Tifei Yuan, Christian Lüscher, Francois Georges, Camilla Bellone
: Potentiation of excitatory inputs onto dopamine neurons of the ventral tegmental area (VTA) induced by cocaine exposure allows remodeling of the mesocorticolimbic circuitry, which ultimately drives drug-adaptive behavior. This potentiation is mediated by changes in NMDAR and AMPAR subunit composition. It remains unknown how this synaptic plasticity affects the activity of dopamine neurons. Here, using rodents, we demonstrate that a single cocaine injection increases the firing rate and bursting activity of VTA dopamine neurons, and that these increases persist for 7 d...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27560295/ionotropic-glutamate-receptors-which-ones-when-and-where-in-the-mammalian-neocortex
#2
Minela Hadzic, Alexander Jack, Petra Wahle
A multitude of 18 iGluR receptor subunits, many of which are diversified by splicing and RNA editing, localize to >20 excitatory and inhibitory neocortical neuron types defined by physiology, morphology and transcriptome, besides various types of glial, endothelial and blood cells. Here, we have compiled the published expression of iGluR subunits in the areas and cell types of developing and adult cortex of rat, mouse, carnivore, bovine, monkey, and human as determined with antibody- and mRNA-based techniques...
August 25, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27558536/emerging-roles-of-glun3-containing-nmda-receptors-in-the-cns
#3
Isabel Pérez-Otaño, Rylan S Larsen, John F Wesseling
GluN3-containing NMDA receptors (GluN3-NMDARs) are rarer than the 'classical' NMDARs, which are composed solely of GluN1 and GluN2 subunits, and have non-conventional biophysical, trafficking and signalling properties. In the CNS, they seem to have important roles in delaying synapse maturation until the arrival of sensory experience and in targeting non-used synapses for pruning. The reactivation of GluN3A expression at inappropriate ages may underlie maladaptive synaptic rearrangements observed in addiction, neurodegenerative diseases and other major brain disorders...
October 2016: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/27525575/cardiac-n-methyl-d-aspartate-receptors-as-a-pharmacological-target
#4
Asya Makhro, Qinghai Tian, Lars Kaestner, Dmitry Kosenkov, Giuseppe Faggian, Max Gassmann, Colin Schwarzwald, Anna Bogdanova
This study focuses on characterization of the cardiac N-methyl D-aspartate receptors (NMDARs) as a target for endogenous and synthetic agonists and antagonists. Using isolated perfused rat hearts, we have shown that intracoronary administration of the NMDAR agonists and antagonists has a pronounced effect on autonomous heart function. Perfusion of rat hearts with autologous blood supplemented with NMDAR agonists was associated with induction of tachycardia, sinus arrhythmia and ischemia occurring within physiological plasma concentration range for glutamate and glycine...
August 10, 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/27072890/glun3a-promotes-nmda-spiking-by-enhancing-synaptic-transmission-in-huntington-s-disease-models
#5
Kashif Mahfooz, Sonia Marco, Rebeca Martínez-Turrillas, Mathan K Raja, Isabel Pérez-Otaño, John F Wesseling
Age-inappropriate expression of juvenile NMDA receptors (NMDARs) containing GluN3A subunits has been linked to synapse loss and death of spiny projection neurons of the striatum (SPNs) in Huntington's disease (HD). Here we show that suppressing GluN3A expression prevents a multivariate synaptic transmission phenotype that precedes morphological signs at early prodromal stages. We start by confirming that afferent fiber stimulation elicits larger synaptic responses mediated by both AMPA receptors and NMDARs in SPNs in the YAC128 mouse model of HD...
September 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27000430/protons-potentiate-glun1-glun3a-currents-by-attenuating-their-desensitisation
#6
Kirstie A Cummings, Gabriela K Popescu
N-methyl-D-aspartate (NMDA) receptors are glutamate- and glycine-gated channels composed of two GluN1 and two GluN2 or/and GluN3 subunits. GluN3A expression is developmentally regulated, and changes in this normal pattern of expression, which occur in several brain disorders, alter synaptic maturation and function by unknown mechanisms. Uniquely within the NMDA receptor family, GluN1/GluN3 receptors produce glycine-gated deeply desensitising currents that are insensitive to glutamate and NMDA; these currents remain poorly characterised and their cellular functions are unknown...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26826701/the-transcription-factor-calcium-response-factor-limits-nmda-receptor-dependent-transcription-in-the-developing-brain
#7
Michelle R Lyons, Liang-Fu Chen, Jie V Deng, Caitlin Finn, Andreas R Pfenning, Aditi Sabhlok, Kelli M Wilson, Anne E West
Neuronal activity sculpts brain development by inducing the transcription of genes such as brain-derived neurotrophic factor (Bdnf) that modulate the function of synapses. Sensory experience is transduced into changes in gene transcription via the activation of calcium signaling pathways downstream of both L-type voltage-gated calcium channels (L-VGCCs) and NMDA-type glutamate receptors (NMDARs). These signaling pathways converge on the regulation of transcription factors including calcium-response factor (CaRF)...
April 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/26777280/the-n-terminal-domain-of-the-glun3a-subunit-determines-the-efficacy-of-glycine-activated-nmda-receptors
#8
Ivana Mesic, Christian Madry, Kirsten Geider, Max Bernhard, Heinrich Betz, Bodo Laube
N-methyl-d-aspartate (NMDA) receptors composed of glycine-binding GluN1 and GluN3 subunits function as excitatory glycine receptors that respond to agonist application only with a very low efficacy. Binding of glycine to the high-affinity GluN3 subunits triggers channel opening, whereas glycine binding to the low-affinity GluN1 subunits causes an auto-inhibition of the maximal glycine-inducible receptor current (Imax). Hence, competitive antagonists of the GluN1 subunit strongly potentiate glycine responses of wild type (wt) GluN1/GluN3 receptors...
June 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26700428/ontogenic-profile-and-synaptic-distribution-of-glun3-proteins-in-the-rat-brain-and-hippocampal-neurons
#9
Karen Siaw-Ling Wee, Francis Chee Kuan Tan, Yoke-Ping Cheong, Sanjay Khanna, Chian-Ming Low
N-Methyl-D-aspartate receptors are localized to synaptic and extrasynaptic sites of dendritic spines and shafts. Here, the ontogenic profiles of GluN3A and GluN3B subunits in the rat brain were determined. A developmental switch from GluN3A to GluN3B proteins was detected within the first two postnatal weeks of crude synaptosomes prepared from forebrain and midbrain. Further fractionation of crude synaptosomes revealed the preferential localization of GluN3B to synaptic regions from P7 onwards. Immunolabeling and biochemical fractionation of rat P7 cultured hippocampal neurons showed that GluN3B was predominantly at synaptic sites...
February 2016: Neurochemical Research
https://www.readbyqxmd.com/read/26515690/the-molecular-physiology-of-the-axo-myelinic-synapse
#10
Ileana Micu, Jason R Plemel, Celia Lachance, Juliane Proft, Andrew J Jansen, Karen Cummins, Jan van Minnen, Peter K Stys
Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling from axon to myelin. 2-Photon microscopy was used to image Ca(2+) changes in myelin in response to electrical stimulation of optic nerve axons ex vivo. We show that optic nerve myelin responds to axonal action potentials by a rise in Ca(2+) levels mediated by GluN2D and GluN3A-containing NMDA receptors...
February 2016: Experimental Neurology
https://www.readbyqxmd.com/read/26441533/neonatal-seizures-alter-nmda-glutamate-receptor-glun2a-and-3a-subunit-expression-and-function-in-hippocampal-ca1-neurons
#11
Chengwen Zhou, Hongyu Sun, Peter M Klein, Frances E Jensen
Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function...
2015: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/26374431/differential-effects-of-pharmacologic-and-genetic-modulation-of-nmda-receptor-activity-on-hiv-gp120-induced-neuronal-damage-in-an-in-vivo-mouse-model
#12
Nobuki Nakanishi, Yeon-Joo Kang, Shichun Tu, Scott R McKercher, Eliezer Masliah, Stuart A Lipton
HIV-associated neurocognitive disorder (HAND) consists of motor and cognitive dysfunction in a relatively large percentage of patients with AIDS. Prior work has suggested that at least part of the neuronal and synaptic damage observed in HAND may occur due to excessive stimulation of NMDA-type glutamate receptors (NMDARs). Here, we compared pharmacological and genetic manipulation of NMDAR activity using an improved derivative of the NMDAR antagonist memantine, termed NitroMemantine, and the modulatory NMDAR subunit GluN3A in the HIV/gp120 transgenic (tg) mouse model of HAND...
January 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/26334321/expression-of-the-nmda-receptor-subunit-glun3a-nr3a-in-the-olfactory-system-and-its-regulatory-role-on-olfaction-in-the-adult-mouse
#13
Jin Hwan Lee, Ling Wei, Todd C Deveau, Xiaohuan Gu, Shan Ping Yu
Glutamate is an excitatory neurotransmitter in the olfactory system and its N-methyl-D-aspartate-(NMDA) receptor subunits [GluN1 (NR1), GluN2A (NR2A), and GluN2B (NR2B)] are expressed at synapses in the olfactory bulb and olfactory epithelium. Thus, glutamatergic neurons and NMDA receptors play key roles in olfaction. GluN3A (NR3A) is a unique inhibitory subunit in the NMDA receptor complex; however, the expression and functional role of GluN3A in the olfactory bulb and epithelium remain unclear. The present study examined the expression patterns of GluN3A in the olfactory bulb and epithelium and explored its functional role in the olfactory system...
July 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/25994914/quantitative-analysis-of-glutamate-receptors-in-glial-cells-from-the-cortex-of-gfap-egfp-mice-following-ischemic-injury-focus-on-nmda-receptors
#14
David Dzamba, Pavel Honsa, Martin Valny, Jan Kriska, Lukas Valihrach, Vendula Novosadova, Mikael Kubista, Miroslava Anderova
Cortical glial cells contain both ionotropic and metabotropic glutamate receptors. Despite several efforts, a comprehensive analysis of the entire family of glutamate receptors and their subunits present in glial cells is still missing. Here, we provide an overall picture of the gene expression of ionotropic (AMPA, kainate, NMDA) and the main metabotropic glutamate receptors in cortical glial cells isolated from GFAP/EGFP mice before and after focal cerebral ischemia. Employing single-cell RT-qPCR, we detected the expression of genes encoding subunits of glutamate receptors in GFAP/EGFP-positive (GFAP/EGFP(+)) glial cells in the cortex of young adult mice...
November 2015: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/25817860/specific-roles-of-nmda-receptor-subunits-in-mental-disorders
#15
H Yamamoto, Y Hagino, S Kasai, K Ikeda
N-methyl-D-aspartate (NMDA) receptor plays important roles in learning and memory. NMDA receptors are a tetramer that consists of two glycine-binding subunits GluN1, two glutamate-binding subunits (i.e., GluN2A, GluN2B, GluN2C, and GluN2D), a combination of a GluN2 subunit and glycine-binding GluN3 subunit (i.e., GluN3A or GluN3B), or two GluN3 subunits. Recent studies revealed that the specific expression and distribution of each subunit are deeply involved in neural excitability, plasticity, and synaptic deficits...
2015: Current Molecular Medicine
https://www.readbyqxmd.com/read/25686081/modulation-of-glun3a-expression-in-huntington-disease-a-new-n-methyl-d-aspartate-receptor-based-therapeutic-approach
#16
REVIEW
John F Wesseling, Isabel Pérez-Otaño
Huntington disease (HD) is an inherited neurodegenerative disorder with no cure or effective palliative treatment. An ideal therapy would arrest pathogenesis at early stages before neuronal damage occurs. However, although the genetic mutation that causes HD is known, the molecular chain of events that leads from the mutation to disease is not well understood. Accumulating evidence suggests that synaptic dysregulation may be involved, and the earliest known deficit is hyperfunction of glutamate-type N-methyl-d-aspartate receptors (NMDARs) in the selectively vulnerable medium spiny neurons of the striatum...
April 2015: JAMA Neurology
https://www.readbyqxmd.com/read/25652449/a-neuroprotective-role-of-the-nmda-receptor-subunit-glun3a-nr3a-in-ischemic-stroke-of-the-adult-mouse
#17
Jin Hwan Lee, Zheng Z Wei, Dongdong Chen, Xiaohuan Gu, Ling Wei, Shan Ping Yu
GluN3A or NR3A is a developmentally regulated N-methyl-d-aspartate receptor (NMDAR) subunit, showing a unique inhibitory role that decreases NMDAR current and the receptor-mediated Ca(2+) influx. In the neonatal brain, GluN3A is shown to associate with synaptic maturation and spine formation and plays a neuroprotective role. Its functional role in the adult brain, however, is largely unknown. We tested the hypothesis that, disrespecting the relatively lower expression level of GluN3A in the adult brain, this inhibitory NMDAR subunit shows a protective action against ischemia-induced brain injury...
April 1, 2015: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/25205677/structural-determinants-and-mechanism-of-action-of-a-glun2c-selective-nmda-receptor-positive-allosteric-modulator
#18
Alpa Khatri, Pieter B Burger, Sharon A Swanger, Kasper B Hansen, Sommer Zimmerman, Erkan Karakas, Dennis C Liotta, Hiro Furukawa, James P Snyder, Stephen F Traynelis
NMDA receptors are tetrameric complexes of GluN1, GluN2A-D, and GluN3A-B subunits and are involved in normal brain function and neurologic disorders. We identified a novel class of stereoselective pyrrolidinone (PYD) positive allosteric modulators for GluN2C-containing NMDA receptors, exemplified by methyl 4-(3-acetyl-4-hydroxy-1-[2-(2-methyl-1H-indol-3-yl)ethyl]-5-oxo-2,5-dihydro-1H-pyrrol-2-yl)benzoate. Here we explore the site and mechanism of action of a prototypical analog, PYD-106, which at 30 μM does not alter responses of NMDA receptors containing GluN2A, GluN2B, and GluN2D and has no effect on AMPA [α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid] and kainate receptors...
November 2014: Molecular Pharmacology
https://www.readbyqxmd.com/read/25144876/synapse-specific-control-of-experience-dependent-plasticity-by-presynaptic-nmda-receptors
#19
Rylan S Larsen, Ikuko T Smith, Jayalakshmi Miriyala, Ji Eun Han, Rebekah J Corlew, Spencer L Smith, Benjamin D Philpot
Sensory experience orchestrates the development of cortical circuitry by adaptively modifying neurotransmission and synaptic connectivity. However, the mechanisms underlying these experience-dependent modifications remain elusive. Here we demonstrate that visual experience suppresses a presynaptic NMDA receptor (preNMDAR)-mediated form of timing-dependent long-term depression (tLTD) at visual cortex layer (L) 4-2/3 synapses. This tLTD can be maintained during development, or reinstated in adulthood, by sensory deprivation...
August 20, 2014: Neuron
https://www.readbyqxmd.com/read/25017909/activation-induced-structural-change-in-the-glun1-glun3a-excitatory-glycine-receptor
#20
Dilshan Balasuriya, Hirohide Takahashi, Shyam Srivats, J Michael Edwardson
Unlike GluN2-containing N-methyl-d-aspartate (NMDA) receptors, which require both glycine and glutamate for activation, receptors composed of GluN1 and GluN3 subunits are activated by glycine alone. Here, we used atomic force microscopy (AFM) imaging to examine the response to activation of the GluN1/GluN3A excitatory glycine receptor. GluN1 and GluN3A subunits were shown to interact intimately within transfected tsA 201 cells. Isolated GluN1/GluN3A receptors integrated into lipid bilayers responded to addition of either glycine or d-serine, but not glutamate, with a ∼1 nm reduction in height of the extracellular domain...
August 8, 2014: Biochemical and Biophysical Research Communications
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