Gene Symbol: Gria4
Description: glutamate receptor, ionotropic, AMPA4 (alpha 4)
Alias: GluA4, GluR-D, Glur-4, Glur4, Gluralpha4, spkw1, glutamate receptor 4, AMPA-selective glutamate receptor 4, glutamate receptor channel alpha 4, glutamate receptor ionotropic, AMPA 4, spike wave 1
Species: mouse
Products:     Gria4

Top Publications

  1. Zhang C, Hammassaki Britto D, Britto L, Duvoisin R. Expression of glutamate receptor subunit genes during development of the mouse retina. Neuroreport. 1996;8:335-40 pubmed
    ..The earliest expression was detected at embryonic day 14 (E14) for GluR1, GluR4 and KA-2; all the other subunits were first detected at E16...
  2. Beyer B, Deleuze C, Letts V, Mahaffey C, Boumil R, Lew T, et al. Absence seizures in C3H/HeJ and knockout mice caused by mutation of the AMPA receptor subunit Gria4. Hum Mol Genet. 2008;17:1738-49 pubmed publisher
    ..Here we find that spkw1 is associated with a hypomorphic retroviral-like insertion mutation in the Gria4 gene, encoding one of the four amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) receptor subunits in the ..
  3. Fuchs E, Zivkovic A, Cunningham M, Middleton S, LeBeau F, Bannerman D, et al. Recruitment of parvalbumin-positive interneurons determines hippocampal function and associated behavior. Neuron. 2007;53:591-604 pubmed
    ..These findings directly show the effects of insufficient recruitment of fast-spiking cells at the network and behavioral level and demonstrate the role of this subpopulation for working and episodic-like memory. ..
  4. Frankel W, Beyer B, Maxwell C, Pretel S, Letts V, Siegel S. Development of a new genetic model for absence epilepsy: spike-wave seizures in C3H/He and backcross mice. J Neurosci. 2005;25:3452-8 pubmed
    ..The major C3H determinant of SWDs, spkw1 (spike-wave 1), mapped to chromosome (Chr 9), and together with a C57BL/6J determinant on Chr 8, spkw2, accounted ..
  5. Hashimoto K, Fukaya M, Qiao X, Sakimura K, Watanabe M, Kano M. Impairment of AMPA receptor function in cerebellar granule cells of ataxic mutant mouse stargazer. J Neurosci. 1999;19:6027-36 pubmed
    ..These results suggest that the defect in MF to GC synaptic transmission is a major factor that causes the cerebellar dysfunction in the stg mutant mouse. ..
  6. Nakajima Y, Mochida S, Okawa K, Nakanishi S. Ca2+-dependent release of Munc18-1 from presynaptic mGluRs in short-term facilitation. Proc Natl Acad Sci U S A. 2009;106:18385-9 pubmed publisher
    ..Our findings unite and provide a new insight into receptor signaling and vesicular transport, which are pivotal activities involved in a variety of cellular processes. ..
  7. Gardner S, Takamiya K, Xia J, Suh J, Johnson R, Yu S, et al. Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron. 2005;45:903-15 pubmed
    ..These results demonstrate that PICK1 and NSF dynamically regulate the synaptic delivery of GluR2-containing receptors during CARP and thus regulate the calcium permeability of AMPA receptors at excitatory synapses. ..
  8. Tokuda S, Beyer B, Frankel W. Genetic complexity of absence seizures in substrains of C3H mice. Genes Brain Behav. 2009;8:283-9 pubmed publisher
    ..Previous studies using the C3H/HeJ (HeJ) substrain identified a mutation in the Gria4 gene as a major susceptibility locus...
  9. Chen Z, Kujawa S, Sewell W. Auditory sensitivity regulation via rapid changes in expression of surface AMPA receptors. Nat Neurosci. 2007;10:1238-40 pubmed
    ..Thus we show that AMPA receptor cycling is important for optimizing synaptic transfer at one of the most exacting synapses in the body. ..

More Information


  1. Huang L, Barclay M, Lee K, Peter S, Housley G, Thorne P, et al. Synaptic profiles during neurite extension, refinement and retraction in the developing cochlea. Neural Dev. 2012;7:38 pubmed publisher
    ..The OHC connections are then selectively eliminated, leaving sparse innervation by type II afferent fibres, whilst the type I afferent synapses with IHCs are consolidated...
  2. de Paola V, Arber S, Caroni P. AMPA receptors regulate dynamic equilibrium of presynaptic terminals in mature hippocampal networks. Nat Neurosci. 2003;6:491-500 pubmed
    ..Thus, synaptic activity can make stable presynaptic terminals become dynamic, providing a candidate mechanism to convert experience into changes in network connectivity. ..
  3. Sagata N, Iwaki A, Aramaki T, Takao K, Kura S, Tsuzuki T, et al. Comprehensive behavioural study of GluR4 knockout mice: implication in cognitive function. Genes Brain Behav. 2010;9:899-909 pubmed publisher
    ..The tetrameric AMPA receptor complexes are composed of four subunits, GluR1-4. The GluR4 subunit is highly expressed in the cerebellum and the early postnatal hippocampus and is thought to be involved in ..
  4. Huupponen J, Atanasova T, Taira T, Lauri S. GluA4 subunit of AMPA receptors mediates the early synaptic response to altered network activity in the developing hippocampus. J Neurophysiol. 2016;115:2989-96 pubmed publisher
    ..AMPA receptor subunit GluA4 is expressed in hippocampal pyramidal neurons during early postnatal period and is critical for neonatal long-term ..
  5. Aruscavage P, Bass B. A phylogenetic analysis reveals an unusual sequence conservation within introns involved in RNA editing. RNA. 2000;6:257-69 pubmed
    ..The approximately 600-nt intron 13 of gluR-C was particularly remarkable, showing >94% nucleotide identity between human and chicken, organisms estimated to have diverged 310 million years ago. ..
  6. Tyler A, McGarr T, Beyer B, Frankel W, Carter G. A genetic interaction network model of a complex neurological disease. Genes Brain Behav. 2014;13:831-40 pubmed publisher
    ..These results illustrate the power of CAPE in identifying novel modifier loci and interactions in a complex neurological disease, toward a more comprehensive view of its underlying genetic architecture. ..
  7. Templin J, Bang S, Soiza Reilly M, Berde C, Commons K. Patterned expression of ion channel genes in mouse dorsal raphe nucleus determined with the Allen Mouse Brain Atlas. Brain Res. 2012;1457:1-12 pubmed publisher
    ..The identified genes likely contribute to unique excitable properties of different groups of neurons in the DR and may include novel pharmacologic targets for affective disorders. ..
  8. Fontaine R, Olivier P, Massonneau V, Leroux P, Degos V, Lebon S, et al. Vulnerability of white matter towards antenatal hypoxia is linked to a species-dependent regulation of glutamate receptor subunits. Proc Natl Acad Sci U S A. 2008;105:16779-84 pubmed publisher
    ..Gestational hypoxia may regulate the expression of specific glutamate-receptor subunits in fetal mice but not in fetal rats. Therefore, genetic factors may influence the susceptibility of rodents to WMD. ..
  9. Thomsen C, Hampson D. Contribution of metabotropic glutamate receptor mGluR4 to L-2-[3H]amino-4-phosphonobutyrate binding in mouse brain. J Neurochem. 1999;72:835-40 pubmed
  10. Seifert G, Rehn L, Weber M, Steinhauser C. AMPA receptor subunits expressed by single astrocytes in the juvenile mouse hippocampus. Brain Res Mol Brain Res. 1997;47:286-94 pubmed
    ..Most frequently, we met co-expression of GluR2 and GluR4. This study demonstrates that astrocytes in the hippocampus express a distinct AMPA-R subunit composition which ..
  11. Sakimura K, Morita T, Kushiya E, Mishina M. Primary structure and expression of the gamma 2 subunit of the glutamate receptor channel selective for kainate. Neuron. 1992;8:267-74 pubmed
    ..Expression of the gamma 2 subunit together with the beta 2 subunit in Xenopus oocytes yields functional glutamate receptor channels selective for kainate. ..
  12. Chan W, Yeung C, Chung E, Lau W, Chan Y, Yung K. Differential expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate glutamate receptors in the rat striatum during postnatal development. Neurosignals. 2003;12:302-9 pubmed
    ..The level of GluR2 mRNA was highest in PND21 rats and lowest in adult. The highest level of GluR4 mRNA was detected in rats at PND7...
  13. Paz J, Bryant A, Peng K, Fenno L, Yizhar O, Frankel W, et al. A new mode of corticothalamic transmission revealed in the Gria4(-/-) model of absence epilepsy. Nat Neurosci. 2011;14:1167-73 pubmed publisher
    ..We found a systemic and specific reduction in strength in GluA4-deficient (Gria4(-/-)) mice of one excitatory synapse of the rhythmogenic cortico-thalamo-cortical system, the cortico-nRT ..
  14. Olsen O, Moore K, Fukata M, Kazuta T, Trinidad J, Kauer F, et al. Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J Cell Biol. 2005;170:1127-34 pubmed
    ..These findings are consistent with a model whereby the MALS-CASK-liprin-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone. ..
  15. Wang H, Liu H, Zhang Z. Elimination of redundant synaptic inputs in the absence of synaptic strengthening. J Neurosci. 2011;31:16675-84 pubmed publisher
    ..Deletion of GluA3 or GluA4 caused significant reductions of synaptic AMPAR currents in thalamic neurons at P16-P17, with a greater reduction ..
  16. Matsugami T, Tanemura K, Mieda M, Nakatomi R, Yamada K, Kondo T, et al. From the Cover: Indispensability of the glutamate transporters GLAST and GLT1 to brain development. Proc Natl Acad Sci U S A. 2006;103:12161-6 pubmed
  17. Wickman K, Seldin M, Gendler S, Clapham D. Partial structure, chromosome localization, and expression of the mouse Girk4 gene. Genomics. 1997;40:395-401 pubmed
    ..No detectable levels were observed in skeletal muscle, liver, and testis. The onset of GIRK4 mRNA expression in the developing mouse occurs between Embryonic Days 7 and 11, consistent with the appearance and function of the mouse heart. ..
  18. Yamasaki M, Miyazaki T, Azechi H, Abe M, Natsume R, Hagiwara T, et al. Glutamate receptor ?2 is essential for input pathway-dependent regulation of synaptic AMPAR contents in cerebellar Purkinje cells. J Neurosci. 2011;31:3362-74 pubmed publisher
    ..Furthermore, we found an unexpected twofold increase in labeling density for GluA2 and GluA3, but not GluA4, at PF-interneuron synapses, where we identified low but significant expression of GluR?2...
  19. Kougioumtzidou E, Shimizu T, Hamilton N, Tohyama K, Sprengel R, Monyer H, et al. Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival. elife. 2017;6: pubmed publisher
    ..Murine OPs in white matter express AMPA receptor (AMPAR) subunits GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, which respectively ..
  20. Kaczmarek L, Kossut M, Skangiel Kramska J. Glutamate receptors in cortical plasticity: molecular and cellular biology. Physiol Rev. 1997;77:217-55 pubmed
    ..Functional studies involving either activation or blocking, and effects of such manipulation on cortical plasticity are discussed...
  21. Finn R, Kovács A, Pearce D. Altered glutamate receptor function in the cerebellum of the Ppt1-/- mouse, a murine model of infantile neuronal ceroid lipofuscinosis. J Neurosci Res. 2012;90:367-75 pubmed publisher
    ..Western blotting of surface cross-linked cerebellar samples showed a significantly lower surface level of the GluR4 AMPA receptor subunit in Ppt1(-/-) mice, providing a plausible explanation for the decreased vulnerability of Ppt1(..
  22. Yang Y, Aitoubah J, Lauer A, Nuriya M, Takamiya K, Jia Z, et al. GluA4 is indispensable for driving fast neurotransmission across a high-fidelity central synapse. J Physiol. 2011;589:4209-27 pubmed publisher
    ..Using GluA3 or GluA4 knockout (KO) mice, we investigated these issues at the calyx of Held synapse, which is known as a high-fidelity ..
  23. Favuzzi E, Marques Smith A, Deogracias R, Winterflood C, Sánchez Aguilera A, Mantoan L, et al. Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican. Neuron. 2017;95:639-655.e10 pubmed publisher
    ..These findings uncover a molecular program through which a PNN protein facilitates appropriate behavioral responses to experience by dynamically gating PV+ interneuron function. ..
  24. Georgiadis K, Hirohata S, Seldin M, Apte S. ADAM-TS8, a novel metalloprotease of the ADAM-TS family located on mouse chromosome 9 and human chromosome 11. Genomics. 1999;62:312-5 pubmed
    ..Through analysis of an interspecific backcross panel, we place the Adamts8 locus on mouse chromosome 9 at a consensus position of 11 cM and its human ortholog, recently reported as the METH2 gene, on human chromosome 11q25. ..
  25. Hayashi T, Rumbaugh G, Huganir R. Differential regulation of AMPA receptor subunit trafficking by palmitoylation of two distinct sites. Neuron. 2005;47:709-23 pubmed
    ..These data suggest that regulated palmitoylation of AMPA receptor subunits modulates receptor trafficking and may be important for synaptic plasticity. ..
  26. Sarowar T, Grabrucker S, Föhr K, Mangus K, Eckert M, Bockmann J, et al. Enlarged dendritic spines and pronounced neophobia in mice lacking the PSD protein RICH2. Mol Brain. 2016;9:28 pubmed publisher
  27. Caba ero D, Baker A, Zhou S, Hargett G, Irie T, Xia Y, et al. Pain after discontinuation of morphine treatment is associated with synaptic increase of GluA4-containing AMPAR in the dorsal horn of the spinal cord. Neuropsychopharmacology. 2013;38:1472-84 pubmed publisher homogenates and in postsynaptic density fractions from spinal cord dorsal horns showed an increase in GluA4 expression and phosphorylation in the postsynaptic density after morphine...
  28. Chen N, Pandya N, Koopmans F, Castelo Székelv V, van der Schors R, Smit A, et al. Interaction proteomics reveals brain region-specific AMPA receptor complexes. J Proteome Res. 2014;13:5695-706 pubmed publisher
    ..Depending on the brain region, an interacting protein can be involved in an AMPA and a non-AMPA receptor complex. ..
  29. Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Müller C, et al. High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron. 2012;74:621-33 pubmed publisher
    ..6 and 1 MDa. The additional constituents change the gating properties of AMPARs and provide links to the protein dynamics fundamental for the complex role of AMPARs in formation and operation of glutamatergic synapses. ..
  30. McNamara J, Eubanks J, McPherson J, Wasmuth J, Evans G, Heinemann S. Chromosomal localization of human glutamate receptor genes. J Neurosci. 1992;12:2555-62 pubmed
    ..together with concordance of the chromosomal locales and results of linkage analyses establishes GluR3 and GluR4 as candidate genes for a number of nervous system disorders including the oculocerebral-renal syndrome of Lowe and ..
  31. Morita T, Sakimura K, Kushiya E, Yamazaki M, Meguro H, Araki K, et al. Cloning and functional expression of a cDNA encoding the mouse beta 2 subunit of the kainate-selective glutamate receptor channel. Brain Res Mol Brain Res. 1992;14:143-6 pubmed
    ..The beta 2 subunit has structural characteristics common to the subunits of glutamate-gated ion channels. Expression of the cloned cDNA in Xenopus oocytes yields functional glutamate receptor channels selective for kainate. ..
  32. Todorova M, Mantis J, Le M, Kim C, Seyfried T. Genetic and environmental interactions determine seizure susceptibility in epileptic EL mice. Genes Brain Behav. 2006;5:518-27 pubmed
  33. Sommer B, Kohler M, Sprengel R, Seeburg P. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991;67:11-9 pubmed
    ..This process apparently edits subunit transcripts of the two glutamate receptor classes with different efficiency and selectivity. ..
  34. Frankel W, Mahaffey C, McGarr T, Beyer B, Letts V. Unraveling genetic modifiers in the gria4 mouse model of absence epilepsy. PLoS Genet. 2014;10:e1004454 pubmed publisher
    ..AE and GGE are complex genetic diseases with few causal variants identified to date. Gria4 deficient mice provide a model of AE, one for which the common laboratory inbred strain C3H/HeJ (HeJ) harbors a ..
  35. Sultana A, Nakaya N, Dong L, Abu Asab M, Qian H, Tomarev S. Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice. Exp Neurol. 2014;261:802-11 pubmed publisher
    ..These results suggest that heterodimers of Olfm1 and Olfm2 interact with AMPAR more efficiently than Olfm2 homodimers and that Olfm2 plays a role in the organization of the AMPA receptor complexes. ..
  36. Caputi A, Fuchs E, Allen K, Le Magueresse C, Monyer H. Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity. PLoS ONE. 2012;7:e37318 pubmed publisher
    ..Here we performed viral injections in genetically modified mice to ablate the GluA4 subunit of the AMPA receptor in the hippocampus (GluA4(HC-/-) mice), thereby selectively reducing AMPA receptor-..
  37. Hou G, Zhang Z. NMDA Receptors Regulate the Development of Neuronal Intrinsic Excitability through Cell-Autonomous Mechanisms. Front Cell Neurosci. 2017;11:353 pubmed publisher
    ..Our results demonstrate that NMDARs regulate intrinsic excitability and morphology of thalamic neurons through cell autonomous mechanisms that implicate mTOR signaling. ..
  38. Zhao G, Liu Y, Yi X, Wang Y, Qiao S, Li Z, et al. Curcumin inhibiting Th17 cell differentiation by regulating the metabotropic glutamate receptor-4 expression on dendritic cells. Int Immunopharmacol. 2017;46:80-86 pubmed publisher
    ..Our findings suggest that curcumin might be a potential candidate for Th17 related autoimmune disorders. ..
  39. Xia Y, Welch C, Warden C, Lange E, Fukao T, Lusis A, et al. Assignment of the mouse ataxia-telangiectasia gene (Atm) to mouse chromosome 9. Mamm Genome. 1996;7:554-5 pubmed
  40. Seol M, Kuner T. Ionotropic glutamate receptor GluA4 and T-type calcium channel Cav 3.1 subunits control key aspects of synaptic transmission at the mouse L5B-POm giant synapse. Eur J Neurosci. 2015;42:3033-44 pubmed publisher
    ..Loss of GluA4 almost abolished the EPSC amplitude, strongly delaying the onset of action potential generation, but maintaining ..
  41. Ströh S, Sonntag S, Janssen Bienhold U, Schultz K, Cimiotti K, Weiler R, et al. Cell-specific cre recombinase expression allows selective ablation of glutamate receptors from mouse horizontal cells. PLoS ONE. 2013;8:e83076 pubmed publisher
    ..mice with a mouse line in which exon 11 of the coding sequence for the ionotropic glutamate receptor subunit GluA4 was flanked by two loxP sites (GluA4fl/fl)...
  42. Fukata Y, Tzingounis A, Trinidad J, Fukata M, Burlingame A, Nicoll R, et al. Molecular constituents of neuronal AMPA receptors. J Cell Biol. 2005;169:399-404 pubmed
    ..These studies establish TARPs as the auxiliary components of neuronal AMPARs. ..
  43. Nakanishi S, Nakajima Y, Masu M, Ueda Y, Nakahara K, Watanabe D, et al. Glutamate receptors: brain function and signal transduction. Brain Res Brain Res Rev. 1998;26:230-5 pubmed
    ..Thus, the two closely related mGluR subtypes mediate diverging intracellular signaling in glutamate transmission. ..
  44. Patel N, Hitzemann R. Detection and mapping of quantitative trait loci for haloperidol-induced catalepsy in a C57BL/6J x DBA/2J F2 intercross. Behav Genet. 1999;29:303-10 pubmed
    ..5) in the proximal region of the chromosome. Potential candidate genes in this region include Penk2 and Gria4. Overall, these data support our previous observation (Kanes et al...
  45. Holst B, Vanderklish P, Krushel L, Zhou W, Langdon R, McWhirter J, et al. Allosteric modulation of AMPA-type glutamate receptors increases activity of the promoter for the neural cell adhesion molecule, N-CAM. Proc Natl Acad Sci U S A. 1998;95:2597-602 pubmed
  46. Luchkina N, Huupponen J, Clarke V, Coleman S, Keinanen K, Taira T, et al. Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors. Proc Natl Acad Sci U S A. 2014;111:4321-6 pubmed publisher
    The AMPA-receptor subunit GluA4 is expressed transiently in CA1 pyramidal neurons at the time synaptic connectivity is forming, but its physiological significance is unknown...
  47. Yamasaki M, Fukaya M, Yamazaki M, Azechi H, Natsume R, Abe M, et al. TARP ?-2 and ?-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area. J Neurosci. 2016;36:4296-312 pubmed publisher
    ..In comparison, TARP ?-8 is the only TARP expressed at nonperforated type of pyramidal cell synapses, playing an essential role in low-density or basal AMPAR expression. ..
  48. Saab A, Neumeyer A, Jahn H, Cupido A, Simek A, Boele H, et al. Bergmann glial AMPA receptors are required for fine motor coordination. Science. 2012;337:749-53 pubmed publisher
    ..acid (AMPA)-type glutamate receptors (AMPARs) composed exclusively of GluA1 and/or GluA4 subunits...
  49. Davis M, Haley T, Duvoisin R, Raber J. Measures of anxiety, sensorimotor function, and memory in male and female mGluR4⁻/⁻ mice. Behav Brain Res. 2012;229:21-8 pubmed publisher
    ..These data indicate that effects of mGluR4 on sensorimotor function and measures of anxiety, but not cued fear conditioning, are critically modulated by sex and age. ..