title: Lack of NMDA receptor subtype selectivity for hippocampal long-term potentiation.
abstract: NMDA receptor (NMDAR) 2A (NR2A)- and NR2B-type NMDARs coexist in synapses of CA1 pyramidal cells. Recent studies using pharmacological blockade of NMDAR subtypes proposed that the NR2A type is responsible for inducing long-term potentiation (LTP), whereas the NR2B type induces long-term depression (LTD). This contrasts with the finding in genetically modified mice that NR2B-type NMDARs induce LTP when NR2A signaling is absent or impaired, although compensatory mechanisms might have contributed to this result. We therefore assessed the contribution of the two NMDAR subtypes to LTP in mouse hippocampal slices by different induction protocols and in the presence of NMDAR antagonists, including the NR2A-type blocker NVP-AAM077, for which an optimal concentration for subtype selectivity was determined on recombinant and native NMDARs. Partial blockade of NMDA EPSCs by 40%, either by preferentially antagonizing NR2A- or NR2B-type NMDARs or by the nonselective antagonist D-AP-5, did not impair LTP, demonstrating that hippocampal LTP induction can be generated by either NMDAR subtype.
authors: Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany.
authors: Sven
authors: S
authors: Berberich
authors: Pradeep
authors: P
authors: Punnakkal
authors: Vidar
authors: V
authors: Jensen
authors: Verena
authors: V
authors: Pawlak
authors: Peter H
authors: PH
authors: Seeburg
authors: Øivind
authors: Ø
authors: Hvalby
authors: Georg
authors: G
authors: Köhr
mesh_terms: D000818:Animals; D002460:Cell Line; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics; D014162:Transfection
chemical_list: C498554:5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010880:Piperidines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C095106:traxoprodil mesylate