Selective subunit antagonists suggest an inhibitory relationship between NR2B and NR2A-subunit containing N-methyl-D: -aspartate receptors in hippocampal slices - PubMed (original) (raw)
. 2005 Apr;162(3):374-83.
doi: 10.1007/s00221-004-2193-6. Epub 2004 Dec 3.
Affiliations
- PMID: 15580338
- DOI: 10.1007/s00221-004-2193-6
Selective subunit antagonists suggest an inhibitory relationship between NR2B and NR2A-subunit containing N-methyl-D: -aspartate receptors in hippocampal slices
Andrew P Mallon et al. Exp Brain Res. 2005 Apr.
Abstract
Glutamate receptors responding to N-methyl-D: -aspartate (NMDA) are involved in neural development, excitotoxicity and neuronal plasticity. Each receptor includes at least two NR2 subunits. Here, we have examined the effects of selective antagonists of NR2A and NR2B subunits (NVP-AAM07 and Ro25-6981 respectively) on the effects of NMDA in the CA1 field of rat hippocampal slices. We have observed that Ro25-6981 potentiates, rather than blocks, the effects of NMD on field EPSPs and paired-pulse interactions (indicators of presynaptic effects) and on postsynaptic depolarisation in hippocampal slices. The NR2A subunit antagonist NVP-AAM077 blocks the effects of NMDA alone, or after potentiation by Ro25-6981. The potentiation of NMDA by Ro25-6981 was not prevented by staurosporine (protein kinase inhibitor), okadaic acid (an inhibitor of serine/threonine protein phosphatases) or anisomycin (protein synthesis inhibitor), but was prevented by cyclosporin A, which inhibits Ca2+/calmodulin-dependent phosphatase 2B [calcineurin]. NMDA-dependent long-term potentiation (LTP) induced by electrical stimulation was not prevented by Ro25-6981 but was prevented by selective blockade of the NR2A subunit. The results suggest that, at both presynaptic and postsynaptic sites in the rat hippocampus, NR2B-subunit-containing receptors limit NMDA receptor function by inhibitory restraint over NR2A-subunit-containing receptors, via calcineurin activation, and that LTP induction critically involves primarily receptors containing the NR2A subunit. Endogenous factors or drugs that modify this NR2B/NR2A interaction could have a major influence on synaptic transmission and plasticity in the brain.
Similar articles
- Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus.
Bartlett TE, Bannister NJ, Collett VJ, Dargan SL, Massey PV, Bortolotto ZA, Fitzjohn SM, Bashir ZI, Collingridge GL, Lodge D. Bartlett TE, et al. Neuropharmacology. 2007 Jan;52(1):60-70. doi: 10.1016/j.neuropharm.2006.07.013. Epub 2006 Aug 10. Neuropharmacology. 2007. PMID: 16904707 - N-methyl-D-aspartate receptor-dependent long-term potentiation in CA1 region affects synaptic expression of glutamate receptor subunits and associated proteins in the whole hippocampus.
Zhong WX, Dong ZF, Tian M, Cao J, Xu L, Luo JH. Zhong WX, et al. Neuroscience. 2006 Sep 1;141(3):1399-413. doi: 10.1016/j.neuroscience.2006.04.070. Epub 2006 Jun 12. Neuroscience. 2006. PMID: 16766131 - Late phase of long-term potentiation induced by co-application of N-methyl-d-aspartic acid and the antagonist of NR2B-containing N-methyl-d-aspartic acid receptors in rat hippocampus.
Oh-Nishi A, Saji M, Satoh SZ, Ogata M, Suzuki N. Oh-Nishi A, et al. Neuroscience. 2009 Mar 3;159(1):127-35. doi: 10.1016/j.neuroscience.2008.10.037. Epub 2008 Oct 30. Neuroscience. 2009. PMID: 19010396 - Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors.
MacDonald JF, Jackson MF, Beazely MA. MacDonald JF, et al. Crit Rev Neurobiol. 2006;18(1-2):71-84. doi: 10.1615/critrevneurobiol.v18.i1-2.80. Crit Rev Neurobiol. 2006. PMID: 17725510 Review. - Group I mGluR Induced LTD of NMDAR-synaptic Transmission at the Schaffer Collateral but not Temperoammonic Input to CA1.
Fitzjohn S, Bashir Z, Farrow P. Fitzjohn S, et al. Curr Neuropharmacol. 2016;14(5):435-40. doi: 10.2174/1570159x13666150615221502. Curr Neuropharmacol. 2016. PMID: 27296639 Free PMC article. Review.
Cited by
- Pharmacological isolation of postsynaptic currents mediated by NR2A- and NR2B-containing NMDA receptors in the anterior cingulate cortex.
Wu LJ, Xu H, Ren M, Cao X, Zhuo M. Wu LJ, et al. Mol Pain. 2007 Apr 30;3:11. doi: 10.1186/1744-8069-3-11. Mol Pain. 2007. PMID: 17470281 Free PMC article. - Activation of NR2A receptors induces ischemic tolerance through CREB signaling.
Terasaki Y, Sasaki T, Yagita Y, Okazaki S, Sugiyama Y, Oyama N, Omura-Matsuoka E, Sakoda S, Kitagawa K. Terasaki Y, et al. J Cereb Blood Flow Metab. 2010 Aug;30(8):1441-9. doi: 10.1038/jcbfm.2010.18. Epub 2010 Feb 10. J Cereb Blood Flow Metab. 2010. PMID: 20145658 Free PMC article. - Redistribution of ionotropic glutamate receptors detected by laser microdissection of the rat dentate gyrus 48 h following LTP induction in vivo.
Kennard JT, Guévremont D, Mason-Parker SE, Abraham WC, Williams JM. Kennard JT, et al. PLoS One. 2014 Mar 25;9(3):e92972. doi: 10.1371/journal.pone.0092972. eCollection 2014. PLoS One. 2014. PMID: 24667777 Free PMC article. - Dissociable effects of NR2A and NR2B NMDA receptor antagonism on cognitive flexibility but not pattern separation.
Kumar G, Olley J, Steckler T, Talpos J. Kumar G, et al. Psychopharmacology (Berl). 2015 Nov;232(21-22):3991-4003. doi: 10.1007/s00213-015-4008-9. Epub 2015 Jul 18. Psychopharmacology (Berl). 2015. PMID: 26184010 - Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity.
Li R, Huang FS, Abbas AK, Wigström H. Li R, et al. BMC Neurosci. 2007 Jul 26;8:55. doi: 10.1186/1471-2202-8-55. BMC Neurosci. 2007. PMID: 17655746 Free PMC article.
References
- J Physiol. 1996 Dec 15;497 ( Pt 3):761-72 - PubMed
- J Gen Physiol. 1997 Nov;110(5):485-502 - PubMed
- Eur J Pharmacol. 1990 Aug 21;185(1):115-7 - PubMed
- Neuroreport. 1998 Jan 26;9(2):327-31 - PubMed
- Science. 1998 Jun 5;280(5369):1596-9 - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous