RGD Reference Report - Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus. - Rat Genome Database

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Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus.

Authors: Bartlett, TE  Bannister, NJ  Collett, VJ  Dargan, SL  Massey, PV  Bortolotto, ZA  Fitzjohn, SM  Bashir, ZI  Collingridge, GL  Lodge, D 
Citation: Bartlett TE, etal., Neuropharmacology. 2007 Jan;52(1):60-70. Epub 2006 Aug 10.
RGD ID: 1642207
Pubmed: PMID:16904707   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuropharm.2006.07.013   (Journal Full-text)

The role of NMDA receptors in the induction of long-term potentiation (LTP) and long-term depression (LTD) is well established but which particular NR2 subunits are involved in these plasticity processes is still a matter of controversy. We have studied the effects of subtype selective NMDA receptor antagonists on LTP induced by high frequency stimulation (100 Hz for 1s) and LTD induced by low frequency stimulation (1 Hz for 15 min) in the CA1 region of hippocampal slices from 14 day old Wistar rats. Against recombinant receptors in HEK293 cells NVP-AAM077 (NVP) was approximately 14-fold selective for NR2A vs NR2B receptors, whilst Ro 25-6981 (Ro) was highly selective for NR2B receptors. On NMDA receptor-mediated EPSCs from Schaffer collaterals in CA1 neurones, NVP and Ro both reduced the amplitude but differentially affected the time constant of decay. The data are compatible with the selective effect of NVP (0.1 microM) and Ro (4 microM) on native NR2A and NBR2B receptors, respectively. NVP reduced both LTP and LTD whereas Ro reduced only LTP. Thus, LTP was reduced by 63% at 0.1 microM NVP and almost completely at 0.4 microM whereas 5 microM Ro reduced LTP by 45%. These data are consistent with a role for both NR2A and NR2B in the induction of LTP, under our experimental conditions. In comparison, LTD was unaffected by Ro (5 microM) even in the presence of a glutamate uptake inhibitor threo-beta-benzylaspartic acid (TBOA) to increase the concentration of glutamate at NR2B containing receptors. NVP (0.2-0.4 microM), however, produced a concentration dependent inhibition of LTD which was complete at 0.4 microM. The lack of effect of 0.1 microM NVP on LTD contrasts with its marked effect on LTP and raises the possibility that different NVP-sensitive NR2 subunit-containing NMDA receptors are required for LTP and LTD in this preparation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
action potential  IMP 1642207; 1642207 RGD 
regulation of long-term neuronal synaptic plasticity  IMP 1642207; 1642207 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Grin2a  (glutamate ionotropic receptor NMDA type subunit 2A)
Grin2b  (glutamate ionotropic receptor NMDA type subunit 2B)

Genes (Mus musculus)
Grin2a  (glutamate receptor, ionotropic, NMDA2A (epsilon 1))
Grin2b  (glutamate receptor, ionotropic, NMDA2B (epsilon 2))

Genes (Homo sapiens)
GRIN2A  (glutamate ionotropic receptor NMDA type subunit 2A)
GRIN2B  (glutamate ionotropic receptor NMDA type subunit 2B)


Additional Information