Differential Calcium-Dependent Modulation of NMDA Currents in CA1 and CA3 Hippocampal Pyramidal Cells

Grishin, Anton A; Gee, Christine E.; Gerber, Urs; Benquet, Pascal

doi:10.1523/jneurosci.4933-03.2004

Cited by 44 publications

(41 citation statements)

References 27 publications

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“…For example, activation of group I mGlu receptors potentiated NMDA receptor currents in CA1 pyramidal cells, but inhibited NMDA receptor currents in nearby hippocampal CA3 pyramidal cells through a Ca 21 -dependent mechanism (Grishin et al, 2004), pointing to cell-specific regulation of NMDA receptors by mGlu receptors. Activation of mGlu7 is reported to inhibit NMDAR currents in neurons of the prefrontal cortex by engaging a b-arrestin/extracellular signal-regulated kinase pathway, which regulates NMDAR surface trafficking by controlling the polymerization state of actin (Gu et al, 2012).…”

Section: Nmda Receptor Modulationmentioning

confidence: 99%

Ionotropic Glutamate Receptors: Regulation by G-Protein-Coupled Receptors

Rojas

Dingledine

2013

Mol Pharmacol

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The function of many ion channels is under dynamic control by coincident activation of G-protein-coupled receptors (GPCRs), particularly those coupled to the G as and G aq family members. Such regulation is typically dependent on the subunit composition of the ionotropic receptor or channel as well as the GPCR subtype and the cell-specific panoply of signaling pathways available. Because GPCRs and ion channels are so highly represented among targets of U.S. Food and Drug Administration-approved drugs, functional cross-talk between these drug target classes is likely to underlie many therapeutic and adverse effects of marketed drugs. GPCRs engage a myriad of signaling pathways that involve protein kinases A and C (PKC) and, through PKC and interaction with b-arrestin, Src kinase, and hence the mitogen-activated-protein-kinase cascades. We focus here on the control of ionotropic glutamate receptor function by GPCR signaling because this form of regulation can influence the strength of synaptic plasticity. The amino acid residues phosphorylated by specific kinases have been securely identified in many ionotropic glutamate (iGlu) receptor subunits, but which of these sites are GPCR targets is less well known even when the kinase has been identified. N-methyl-D-aspartate, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and heteromeric kainate receptors are all downstream targets of GPCR signaling pathways. The details of GPCR-iGlu receptor cross-talk should inform a better understanding of how synaptic transmission is regulated and lead to new therapeutic strategies for neuropsychiatric disorders.

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Section: Nmda Receptor Modulationmentioning

confidence: 99%

Ionotropic Glutamate Receptors: Regulation by G-Protein-Coupled Receptors

Rojas

Dingledine

2013

Mol Pharmacol

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“…Exogenous NMDA-evoked currents are typically transiently potentiated by group I mGluR activation (Benquet et al 2002;Grishin et al 2004;Heidinger et al 2002;Mannaioni et al 2001;Skeberdis et al 2001;Snyder et al 2001). This involves G protein-mediated activation of phospholipase C (PLC) , release of calcium from inositol triphosphate (IP3)-sensitive calcium stores, and activation of protein kinase C (PKC) (Benquet et al 2002;Skeberdis et al 2001) and src family tyrosine kinases (Benquet et al 2002;Heidinger et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Group I mGluR-Dependent Long-Term Depression of NMDA Receptor–Mediated Transmission at Schaffer Collateral–CA1 Synapses

Ireland¹,

Abraham²

2009

Journal of Neurophysiology

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Ireland DR, Abraham WC. Mechanisms of group I mGluR-dependent long-term depression of NMDA receptor-mediated transmission at Schaffer collateral-CA1 synapses. J Neurophysiol 101: 1375-1385, 2009. First published December 24, 2008 doi:10.1152/jn.90643.2008. The mechanisms underlying group I metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) of N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents (EPSCs NMDAR ) are poorly understood. Here we investigated the effects of (R,S)-3,5-dihydroxyphenylglycine (DHPG), a selective agonist of group I mGluRs, on the EPSCs NMDAR in area CA1 of acute hippocampal slices from 6-to 8-wk Sprague-Dawley rats. DHPG acutely and persistently depressed the isolated EPSC NMDAR and transiently slowed its decay rate. Combined antagonism of mGluR1 and mGluR5 blocked the effects of DHPG. Strong calcium buffering with intracellular BAPTA did not reduce the acute depression or LTD, making the involvement of elevated postsynaptic calcium unlikely. The acute depression and LTD were not mediated by activation of tyrosine kinases or phosphatases, nor were they dependent on protein synthesis. However, the LTD was prevented by the intracellular actin-stabilizer jasplakinolide, raising the possibility that it was associated with a lateral movement of NMDARs. Supporting this hypothesis, when the effective spatial spread of synaptically released glutamate was increased using the glutamate transporter inhibitor TBOA, the resultant EPSC NMDAR did not undergo LTD in response to DHPG. Importantly, isolation of the extrasynaptic EPSC NMDAR by blockade of synaptic NMDARs with MK-801 showed that this was not due to a potentiation of the preexisting extrasynaptic component. These findings indicate that LTD of NMDAR-mediated synaptic transmission occurs via lateral movement of receptors away from the synapse.

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“…The statistical significance of a drug's effect was determined by comparing measures before and after drug injection using ANOVA followed by a post-hoc Tukey test [20] . Although both Hal and Cloz inhibited the function of the NR1a/NR2B receptor, their effects were not entirely identified.…”

Section: Methodsmentioning

confidence: 99%

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

Shen

Shi

et al. 2007

Acta Pharmacologica Sinica

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Aim: To examine whether (-)-stepholidine (SPD) has a direct effect on the Nmethyl-D-aspartic acid receptors (NMDAR) containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol (Hal) and clozapine (Cloz). Methods: NMDAR was transiently expressed in human embryonic kidney 293 (HEK293) cells. Changes in intracellular calcium concentration ([Ca 2+ ] i ) induced by NMDAR activation were monitored with Fura-2 ratio imaging techniques. Results: SPD had no significant effects on either subunit of NMDAR at a concentration of less than 100 µmol/L. Hal selectively inhibited NMDAR containing the NR2B subunit, whereas Cloz inhibited both subunits of NMDAR. Although both Hal and Cloz inhibited NR1a/NR2B receptor-mediated Ca 2+ influx, their effects were different. Hal was more potent and had a faster peak effect than Cloz. Conclusion: Both Hal and Cloz inhibit NMDAR-mediated function, whereas SPD produced only a little inhibition at a high concentration. Based on our other studies, the modulation of SPD on NMDAR function may be via D 1 receptor action underlying an indirect mechanism.

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Differential Calcium-Dependent Modulation of NMDA Currents in CA1 and CA3 Hippocampal Pyramidal Cells

Cited by 44 publications

References 27 publications

Ionotropic Glutamate Receptors: Regulation by G-Protein-Coupled Receptors

Ionotropic Glutamate Receptors: Regulation by G-Protein-Coupled Receptors

Mechanisms of Group I mGluR-Dependent Long-Term Depression of NMDA Receptor–Mediated Transmission at Schaffer Collateral–CA1 Synapses

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

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