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Deletion of the C-terminal domain of the NR2B subunit alters channel properties and synaptic targeting of N-methyl-D-aspartate receptors in nascent neocortical synapses.
J Neurosci Res. 2002 May 01; 68(3):265-75.JN

Abstract

Channel properties and synaptic targeting of N-methyl-D-aspartate (NMDA) receptors determine their importance in synaptic transmission, long-term synaptic plasticity, and developmental reorganization of synaptic circuits. To investigate the involvement of the C-terminal domain of the NR2B subunit in regulating channel properties and synaptic localization, we analyzed gene-targeted mice expressing C-terminally truncated NR2B subunits (NR2B(DeltaC/DeltaC) mice; Sprengel et al. [1998] Cell 92:279-89). Because homozygous NR2B(DeltaC/DeltaC) mice die perinatally, we studied embryonic neocortical neurons differentiating in culture. At early stages in vitro, neurons predominantly expressed NR1/NR2B receptors, as shown by the NR2B subunit-specific antagonist ifenprodil. At these nascent synapses, NMDA excitatory postsynaptic currents (EPSCs) in neurons from NR2B(DeltaC/DeltaC) mice showed a strong-amplitude reduction to 20% of control, but AMPA EPSCs were unaltered. Analysis of the MK-801 block of NMDA receptor-mediated whole-cell currents revealed a decreased peak open probability of NMDA receptor channels (to about 60%) in neurons from NR2B(DeltaC/DeltaC) mice, although their single channel conductance was unchanged. To study effects on synaptic targeting, we determined the fraction of synaptically localized NMDA receptors relative to the whole-cell NMDA receptor population. In neurons from NR2B(DeltaC/DeltaC) mice, the synaptic NMDA receptor fraction was drastically reduced, suggesting that the C-terminal domain of the NR2B subunit plays a major role in synaptic targeting of NMDA receptors at nascent synapses. With increasing time in culture, the reduction in NMDA EPSCs in neurons from NR2B(DeltaC/DeltaC) mice diminished. This is explained by the expression of additional NMDA receptor subtypes containing NR2A subunits at more mature synapses.

Authors+Show Affiliations

Mohrmann R
Lehrstuhl für Zellphysiologie, Ruhr-Universität Bochum, Bochum, Germany.
Köhr G
No affiliation info available
Hatt H
No affiliation info available
Sprengel R
No affiliation info available
Gottmann K
No affiliation info available

MeSH

AnimalsCell DifferentiationElectric StimulationExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsFemaleFetusGene DeletionGene TargetingGlutamic AcidMiceMice, KnockoutMutationNeocortexNeuronsPiperidinesPregnancyProtein Structure, TertiaryReceptors, AMPAReceptors, N-Methyl-D-AspartateSynapsesSynaptic TransmissionTetrodotoxin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12111856

Citation

Mohrmann, Ralf, et al. "Deletion of the C-terminal Domain of the NR2B Subunit Alters Channel Properties and Synaptic Targeting of N-methyl-D-aspartate Receptors in Nascent Neocortical Synapses." Journal of Neuroscience Research, vol. 68, no. 3, 2002, pp. 265-75.
Mohrmann R, Köhr G, Hatt H, et al. Deletion of the C-terminal domain of the NR2B subunit alters channel properties and synaptic targeting of N-methyl-D-aspartate receptors in nascent neocortical synapses. J Neurosci Res. 2002;68(3):265-75.
Mohrmann, R., Köhr, G., Hatt, H., Sprengel, R., & Gottmann, K. (2002). Deletion of the C-terminal domain of the NR2B subunit alters channel properties and synaptic targeting of N-methyl-D-aspartate receptors in nascent neocortical synapses. Journal of Neuroscience Research, 68(3), 265-75.
Mohrmann R, et al. Deletion of the C-terminal Domain of the NR2B Subunit Alters Channel Properties and Synaptic Targeting of N-methyl-D-aspartate Receptors in Nascent Neocortical Synapses. J Neurosci Res. 2002 May 1;68(3):265-75. PubMed PMID: 12111856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deletion of the C-terminal domain of the NR2B subunit alters channel properties and synaptic targeting of N-methyl-D-aspartate receptors in nascent neocortical synapses. AU - Mohrmann,Ralf, AU - Köhr,Georg, AU - Hatt,Hanns, AU - Sprengel,Rolf, AU - Gottmann,Kurt, PY - 2002/7/12/pubmed PY - 2002/8/22/medline PY - 2002/7/12/entrez SP - 265 EP - 75 JF - Journal of neuroscience research JO - J Neurosci Res VL - 68 IS - 3 N2 - Channel properties and synaptic targeting of N-methyl-D-aspartate (NMDA) receptors determine their importance in synaptic transmission, long-term synaptic plasticity, and developmental reorganization of synaptic circuits. To investigate the involvement of the C-terminal domain of the NR2B subunit in regulating channel properties and synaptic localization, we analyzed gene-targeted mice expressing C-terminally truncated NR2B subunits (NR2B(DeltaC/DeltaC) mice; Sprengel et al. [1998] Cell 92:279-89). Because homozygous NR2B(DeltaC/DeltaC) mice die perinatally, we studied embryonic neocortical neurons differentiating in culture. At early stages in vitro, neurons predominantly expressed NR1/NR2B receptors, as shown by the NR2B subunit-specific antagonist ifenprodil. At these nascent synapses, NMDA excitatory postsynaptic currents (EPSCs) in neurons from NR2B(DeltaC/DeltaC) mice showed a strong-amplitude reduction to 20% of control, but AMPA EPSCs were unaltered. Analysis of the MK-801 block of NMDA receptor-mediated whole-cell currents revealed a decreased peak open probability of NMDA receptor channels (to about 60%) in neurons from NR2B(DeltaC/DeltaC) mice, although their single channel conductance was unchanged. To study effects on synaptic targeting, we determined the fraction of synaptically localized NMDA receptors relative to the whole-cell NMDA receptor population. In neurons from NR2B(DeltaC/DeltaC) mice, the synaptic NMDA receptor fraction was drastically reduced, suggesting that the C-terminal domain of the NR2B subunit plays a major role in synaptic targeting of NMDA receptors at nascent synapses. With increasing time in culture, the reduction in NMDA EPSCs in neurons from NR2B(DeltaC/DeltaC) mice diminished. This is explained by the expression of additional NMDA receptor subtypes containing NR2A subunits at more mature synapses. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/12111856/Deletion_of_the_C_terminal_domain_of_the_NR2B_subunit_alters_channel_properties_and_synaptic_targeting_of_N_methyl_D_aspartate_receptors_in_nascent_neocortical_synapses_ DB - PRIME DP - Unbound Medicine ER -