Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H, M, R, Chp||IHC, IP, WB||Rb||Culture Supernatant||Monoclonal Antibody|
|Presentation||Cultured supernantant in 0.05% sodium azide|
|Safety Information according to GHS|
|Material Size||100 µL|
|Anti-GluR1, clone C3T||2462885|
|Anti-GluR1, clone C3T - 2007357||2007357|
|Anti-GluR1, clone C3T - 2146013||2146013|
|Anti-GluR1, clone C3T - 2452486||2452486|
|Anti-GluR1, clone C3T - NG1845570||NG1845570|
|Anti-GluR1, clone C3T - 2026873||2026873|
|Anti-GluR1, clone C3T - 2294368||2294368|
|Anti-GluR1, clone C3T - DAM1532834||DAM1532834|
|Anti-GluR1, clone C3T - JBC1771111||JBC1771111|
|Anti-GluR1, clone C3T - JBC1771111||JBC1771111|
|Reference overview||Application||Pub Med ID|
|Estrous Cycle-Dependent Phasic Changes in the Stoichiometry of Hippocampal Synaptic AMPA Receptors in Rats.|
Tada, H; Koide, M; Ara, W; Shibata, Y; Funabashi, T; Suyama, K; Goto, T; Takahashi, T
PloS one 10 e0131359 2015
Cognitive function can be affected by the estrous cycle. However, the effect of the estrous cycle on synaptic functions is poorly understood. Here we show that in female rats, inhibitory-avoidance (IA) task (hippocampus-dependent contextual fear-learning task) drives GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) into the hippocampal CA3-CA1 synapses during all periods of the estrous cycle except the proestrous period, when estrogen levels are high. In addition, IA task failed to drive CP-AMPARs into the CA3-CA1 synapses of ovariectomized rats only when estrogen was present. Thus, changes in the stoichiometry of AMPA receptors during learning depend on estrogen levels. Furthermore, the induction of long-term potentiation (LTP) after IA task was prevented during the proestrous period, while intact LTP is still expressed after IA task during other period of the estrous cycle. Consistent with this finding, rats conditioned by IA training failed to acquire hippocampus-dependent Y-maze task during the proestrous period. On the other hand, during other estrous period, rats were able to learn Y-maze task after IA conditioning. These results suggest that high estrogen levels prevent the IA learning-induced delivery of CP-AMPARs into hippocampal CA3-CA1 synapses and limit synaptic plasticity after IA task, thus preventing the acquisition of additional learning.
|Synaptic dysregulation in a human iPS cell model of mental disorders.|
Wen, Z; Nguyen, HN; Guo, Z; Lalli, MA; Wang, X; Su, Y; Kim, NS; Yoon, KJ; Shin, J; Zhang, C; Makri, G; Nauen, D; Yu, H; Guzman, E; Chiang, CH; Yoritomo, N; Kaibuchi, K; Zou, J; Christian, KM; Cheng, L; Ross, CA; Margolis, RL; Chen, G; Kosik, KS; Song, H; Ming, GL
Dysregulated neurodevelopment with altered structural and functional connectivity is believed to underlie many neuropsychiatric disorders, and 'a disease of synapses' is the major hypothesis for the biological basis of schizophrenia. Although this hypothesis has gained indirect support from human post-mortem brain analyses and genetic studies, little is known about the pathophysiology of synapses in patient neurons and how susceptibility genes for mental disorders could lead to synaptic deficits in humans. Genetics of most psychiatric disorders are extremely complex due to multiple susceptibility variants with low penetrance and variable phenotypes. Rare, multiply affected, large families in which a single genetic locus is probably responsible for conferring susceptibility have proven invaluable for the study of complex disorders. Here we generated induced pluripotent stem (iPS) cells from four members of a family in which a frameshift mutation of disrupted in schizophrenia 1 (DISC1) co-segregated with major psychiatric disorders and we further produced different isogenic iPS cell lines via gene editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPS-cell-derived forebrain neurons. Mutant DISC1 depletes wild-type DISC1 protein and, furthermore, dysregulates expression of many genes related to synapses and psychiatric disorders in human forebrain neurons. Our study reveals that a psychiatric disorder relevant mutation causes synapse deficits and transcriptional dysregulation in human neurons and our findings provide new insight into the molecular and synaptic etiopathology of psychiatric disorders.
|STAT1 regulates the homeostatic component of visual cortical plasticity via an AMPA receptor-mediated mechanism.|
Nagakura, I; Van Wart, A; Petravicz, J; Tropea, D; Sur, M
The Journal of neuroscience : the official journal of the Society for Neuroscience 34 10256-63 2014
Accumulating evidence points to a role for Janus kinase/signal transducers and activators of transcription (STAT) immune signaling in neuronal function; however, its role in experience-dependent plasticity is unknown. Here we show that one of its components, STAT1, negatively regulates the homeostatic component of ocular dominance plasticity in visual cortex. After brief monocular deprivation (MD), STAT1 knock-out (KO) mice show an accelerated increase of open-eye responses, to a level comparable with open-eye responses after a longer duration of MD in wild-type (WT) mice. Therefore, this component of plasticity is abnormally enhanced in KO mice. Conversely, increasing STAT1 signaling by IFNγ treatment in WT mice reduces the homeostatic component of plasticity by impairing open-eye responses. Enhanced plasticity in KO mice is accompanied by sustained surface levels of GluA1 AMPA receptors and increased amplitude and frequency of AMPA receptor-mediated mEPSCs, which resemble changes in WT mice after a longer duration of MD. These results demonstrate a unique role for STAT1 during visual cortical plasticity in vivo through a mechanism that includes AMPA receptors.
|Gonadectomy differentially regulates steroid receptor coactivator-1 and synaptic proteins in the hippocampus of adult female and male C57BL/6 mice.|
Chen Bian,Kongjiang Zhu,Li Yang,Sen Lin,Shurong Li,Bingyin Su,Jiqiang Zhang
Synapse (New York, N.Y.) 66 2012
Hippocampus is one of the most important structures that mediates learning and memory, cognition, and mental behaviors and profoundly regulated by sex hormones in a sex-specific manner, but the mechanism of underlying sex differences regulation is still unclear. We have previously reported that in the male and female mice, steroid receptor coactivator-1 (SRC-1) and some key synaptic proteins share similar developmental profile in the hippocampus, but how circulating sex hormones affect hippocampal SRC-1 as well as these synaptic proteins remain unclear. In this study, we examined how gonad sex hormones regulate hippocampal SRC-1, synaptophysin, PSD-95, and AMPA receptor subtype GluR1 by using immunohistochemistry and Western blot. The results showed that in the female mice, ovariectomy affected hippocampal SRC-1 and GluR1 were only detected at 2 weeks post operation, then it recovered to sham level; synaptophysin was unaffected at any timepoint examined; significant decrease of PSD-95 was only detected at 4 weeks post operation. However, in the male hippocampus, SRC-1 and PSD-95 were decreased from one week and lasted to 4 weeks after orchidectomy, GluR1 decreased from 2 weeks after orchidectomy, but synaptophysin remained unchanged as in the females. Correlation analysis showed the profiles of SRC-1 were positively correlated with GluR1 of the females, PSD-95 and GluR1 of the males, respectively. The above results suggested a distinct regulatory mode between female and male gonad hormones in the regulation of hippocampal SRC-1 and synaptic proteins, which may be one of the mechanisms contributing to the dimorphism of hippocampus during development and ageing.
|Ethanol-mediated facilitation of AMPA receptor function in the dorsomedial striatum: implications for alcohol drinking behavior.|
Wang, J; Ben Hamida, S; Darcq, E; Zhu, W; Gibb, SL; Lanfranco, MF; Carnicella, S; Ron, D
The Journal of neuroscience : the official journal of the Society for Neuroscience 32 15124-32 2012
We found previously that acute ex vivo as well as repeated cycles of in vivo ethanol exposure and withdrawal, including excessive voluntary consumption of ethanol, produces a long-lasting increase in the activity of NR2B-containing NMDA receptors (NR2B-NMDARs) in the dorsomedial striatum (DMS) of rats (Wang et al., 2010a). Activation of NMDARs is required for the induction of long-term potentiation (LTP) of AMPA receptor (AMPAR)-mediated synaptic response. We therefore examined whether the ethanol-mediated upregulation of NMDAR activity alters the induction of LTP in the DMS. We found that ex vivo acute exposure of striatal slices to, and withdrawal from, ethanol facilitates the induction of LTP in DMS neurons, which is abolished by the inhibition of NR2B-NMDARs. We also report that repeated systemic administration of ethanol causes an NR2B-NMDAR-dependent facilitation of LTP in the DMS. LTP is mediated by the insertion of AMPAR subunits into the synaptic membrane, and we found that repeated systemic administration of ethanol, as well as cycles of excessive ethanol consumption and withdrawal, produced a long-lasting increase in synaptic localization of the GluR1 and GluR2 subunits of AMPARs in the DMS. Importantly, we report that inhibition of AMPARs in the DMS attenuates operant self-administration of ethanol, but not of sucrose. Together, our data suggest that aberrant synaptic plasticity in the DMS induced by repeated cycles of ethanol exposure and withdrawal contributes to the molecular mechanisms underlying the development and/or maintenance of excessive ethanol consumption.
|Phosphorylation of the alpha-amino-3-hydroxy-5-methylisoxazole4-propionic acid receptor GluR1 subunit by calcium/calmodulin-dependent kinase II.|
Mammen, A L, et al.
J. Biol. Chem., 272: 32528-33 (1997) 1997
Modulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid (AMPA) receptors in the brain by protein phosphorylation may play a crucial role in the regulation of synaptic plasticity. Previous studies have demonstrated that calmodulin (CaM) kinase II can phosphorylate and modulate AMPA receptors. However, the sites of CaM kinase phosphorylation have not been unequivocally identified. In the current study, we have generated two phosphorylation site-specific antibodies to analyze the phosphorylation of the glutamate receptor GluR1 subunit. These antibodies recognize GluR1 only when it is phosphorylated on serine residues 831 or 845. We have used these antibodies to demonstrate that serine 831 is specifically phosphorylated by CaM kinase II in transfected cells expressing GluR1 as well as in hippocampal slice preparations. Two-dimensional phosphopeptide mapping experiments indicate that Ser-831 is the major site of CaM kinase II phosphorylation on GluR1. In addition, treatment of hippocampal slice preparations with phorbol esters and forskolin increase the phosphorylation of serine 831 and 845, respectively, indicating that protein kinase C and protein kinase A phosphorylate these residues in hippocampal slices. These results identify the site of CaM kinase phosphorylation of the GluR1 subunit and demonstrate that GluR1 is multiply phosphorylated by protein kinase A, protein kinase C, and CaM kinase II in situ.
|The striatal mosaic in primates: striosomes and matrix are differentially enriched in ionotropic glutamate receptor subunits.|
Martin, L J, et al.
J. Neurosci., 13: 782-92 (1993) 1993
|The distribution of glutamate receptors in cultured rat hippocampal neurons: postsynaptic clustering of AMPA-selective subunits.|
Craig, A M, et al.
Neuron, 10: 1055-68 (1993) 1993
The distribution of several glutamate receptor subunits was investigated in cultured rat hippocampal neurons by in situ hybridization and immunocytochemistry. The AMPA/kainate-selective receptors GluR1-6 exhibited two patterns of mRNA expression: most neurons expressed GluR1, R2, and R6, whereas only about 20% expressed significant levels of GluR3, R4, and R5. By immunocytochemistry, the metabotropic glutamate receptor mGluR1 alpha was detectable only in a subpopulation of GABAergic interneurons. GluR1 and GluR2/3 segregated to the somatodendritic domain within the first week in culture, even in the absence of synaptogenesis. Glutamate receptor-enriched spines developed later and were present only on presumptive pyramidal cells, not on GABAergic interneurons. Clusters of GluR1 and GluR2/3 completely colocalized and were restricted to a subset of postsynaptic sites. Thus, glutamate receptor subunits exhibit both a cell type-specific expression and a selective subcellular localization.
|Cellular localizations of AMPA glutamate receptors within the basal forebrain magnocellular complex of rat and monkey.|
Martin, L J, et al.
J. Neurosci., 13: 2249-63 (1993) 1993
The cellular distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors within the rodent and nonhuman primate basal forebrain magnocellular complex (BFMC) were demonstrated immunocytochemically using anti-peptide antibodies that recognize glutamate receptor (GluR) subunit proteins (i.e., GluR1, GluR4, and a conserved region of GluR2, GluR3, and GluR4c). In both species, many large GluR1-positive neuronal perikarya and aspiny dendrites are present within the medial septal nucleus, the nucleus of the diagonal band of Broca, and the nucleus basalis of Meynert. In this population of neurons in rat and monkey, GluR2/3/4c and GluR4 immunoreactivities are less abundant than GluR1 immunoreactivity. In rat, GluR1 does not colocalize with ChAT, but, within many neurons, GluR1 does colocalize with GABA, glutamic acid decarboxylase (GAD), and parvalbumin immunoreactivities. GluR1- and GABA/GAD-positive neurons intermingle extensively with ChAT-positive neurons. In monkey, however, most GluR1-immunoreactive neurons express ChAT and calbindin-D28 immunoreactivities. The results reveal that noncholinergic GABAergic neurons, within the BFMC of rat, express AMPA receptors, whereas cholinergic neurons in the BFMC of monkey express AMPA receptors. Thus, the cellular localizations of the AMPA subtype of GluR are different within the BFMC of rat and monkey, suggesting that excitatory synaptic regulation of distinct subsets of BFMC neurons may differ among species. We conclude that, in the rodent, BFMC GABAergic neurons receive glutamatergic inputs, whereas cholinergic neurons either do not receive glutamatergic synapses or utilize GluR subtypes other than AMPA receptors. In contrast, in primate, basal forebrain cholinergic neurons are innervated directly by glutamatergic afferents and utilize AMPA receptors.
|Pathways and Biomarkers of Glutamatergic Synapse Flyer|