title: Triheteromeric NR1/NR2A/NR2B receptors constitute the major NMDA receptor population in adult hippocampal synapses
creator: Rauner, Claudia
subject: ddc-570
subject: 570 Life sciences
description: N-methyl-D-aspartate receptors (NMDARs), fundamental to learning and memory and implicated in certain neurological disorders, are heterotetrameric complexes composed of two NR1 and two NR2 subunits. The role of synaptic NMDARs in postnatal principal forebrain neurons is typically attributed to diheteromeric NR1/NR2A and NR1/NR2B receptors, despite compelling evidence for triheteromeric NR1/NR2A/NR2B receptors. In hippocampal CA1 synapses, the properties of triheteromeric NMDARs could thus far not be distinguished from those of mixtures of diheteromeric NMDARs. To find a signature of NR1/NR2A/NR2B receptors, we have employed two gene-targeted mouse lines, expressing either NR1/NR2A or NR1/NR2B receptors without any NR1/NR2A/NR2B receptors, and compared their synaptic properties to those of wild type. We found in acute hippocampal slices of adult mice a distinct voltage dependence of NMDA EPSC decay time for the two diheteromeric NMDARs. In age-matched wild-type mice, only the NR1/NR2A characteristic for this voltage-dependent deactivation could be detected, indicating that NR1/NR2B receptors are a minor population in adult CA3-to-CA1 synapses. Instead, the presence of NR1/NR2A/NR2B receptors became manifest from a slower NMDA EPSC decay time than for NR1/NR2A receptors. Moreover, we examined the sensitivity of NMDA EPSCs to NR2Bdirected NMDAR antagonists in the absence of extracellular Mg2+, which improved the sensitivity of these antagonists, especially for NR1/NR2A/NR2B receptors. NMDA EPSC sensitivity to NR2B-directed NMDAR antagonists was high at P5 and remained around 50% at P28. Thus, NR2B is prominent in hippocampal synapses throughout life and remains present in adult mice as an integral part of NR1/NR2A/NR2B receptors.
date: 2010
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/10569/1/Dissertation_CR.pdf
identifier: DOI:10.11588/heidok.00010569
identifier: urn:nbn:de:bsz:16-opus-105697
identifier:   Rauner, Claudia  (2010) Triheteromeric NR1/NR2A/NR2B receptors constitute the major NMDA receptor population in adult hippocampal synapses.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/10569/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng