PMID- 25131300
OWN - NLM
STAT- MEDLINE
DCOM- 20150626
LR  - 20181202
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 40
IP  - 8
DP  - 2014 Oct
TI  - The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA 
      receptors in the neonatal mouse brain.
PG  - 3136-46
LID - 10.1111/ejn.12682 [doi]
AB  - The N-methyl-D-aspartate receptor (NMDAR) plays various physiological and 
      pathological roles in neural development, synaptic plasticity and neuronal cell 
      death. It is composed of two GluN1 and two GluN2 subunits and, in the neonatal 
      hippocampus, most synaptic NMDARs are GluN2B-containing receptors, which are 
      gradually replaced with GluN2A-containing receptors during development. Here, we 
      examined whether GluN2A could be substituted for GluN2B in neural development and 
      functions by analysing knock-in (KI) mice in which GluN2B is replaced with 
      GluN2A. The KI mutation was neonatally lethal, although GluN2A-containing 
      receptors were transported to the postsynaptic membrane even without GluN2B and 
      functional at synapses of acute hippocampal slices of postnatal day 0, indicating 
      that GluN2A-containing NMDARs could not be substituted for GluN2B-containing 
      NMDARs. Importantly, the synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole 
      propionic acid receptor (AMPAR) subunit GluA1 was increased, and the 
      transmembrane AMPAR regulatory protein, which is involved in AMPAR synaptic 
      trafficking, was increased in KI mice. Although the regulation of AMPARs by 
      GluN2B has been reported in cultured neurons, we showed here that AMPAR-mediated 
      synaptic responses were increased in acute KI slices, suggesting differential 
      roles of GluN2A and GluN2B in AMPAR expression and trafficking in vivo. Taken 
      together, our results suggest that GluN2B is essential for the survival of 
      animals, and that the GluN2B-GluN2A switching plays a critical role in synaptic 
      integration of AMPARs through regulation of GluA1 in the whole animal.
CI  - (c) 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Hamada, Shun
AU  - Hamada S
AD  - Division of Neuronal Network, Institute of Medical Science, University of Tokyo, 
      Tokyo, 108-8639, Japan.
FAU - Ogawa, Itone
AU  - Ogawa I
FAU - Yamasaki, Miwako
AU  - Yamasaki M
FAU - Kiyama, Yuji
AU  - Kiyama Y
FAU - Kassai, Hidetoshi
AU  - Kassai H
FAU - Watabe, Ayako M
AU  - Watabe AM
FAU - Nakao, Kazuki
AU  - Nakao K
FAU - Aiba, Atsu
AU  - Aiba A
FAU - Watanabe, Masahiko
AU  - Watanabe M
FAU - Manabe, Toshiya
AU  - Manabe T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140808
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - VH92ICR8HX (N-methyl D-aspartate receptor subtype 2A)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/*metabolism
MH  - Gene Knock-In Techniques
MH  - Mice
MH  - Protein Transport
MH  - Receptors, AMPA/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
OTO - NOTNLM
OT  - NMDA receptor
OT  - TARP
OT  - hippocampus
OT  - miniature EPSC
OT  - postsynaptic density
EDAT- 2014/08/19 06:00
MHDA- 2015/06/27 06:00
CRDT- 2014/08/19 06:00
PHST- 2014/05/22 00:00 [received]
PHST- 2014/07/03 00:00 [revised]
PHST- 2014/07/04 00:00 [accepted]
PHST- 2014/08/19 06:00 [entrez]
PHST- 2014/08/19 06:00 [pubmed]
PHST- 2015/06/27 06:00 [medline]
AID - 10.1111/ejn.12682 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2014 Oct;40(8):3136-46. doi: 10.1111/ejn.12682. Epub 2014 Aug 8.