PMID- 12560119
OWN - NLM
STAT- MEDLINE
DCOM- 20030428
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 963
IP  - 1-2
DP  - 2003 Feb 14
TI  - NMDA receptor blockade in intact adult cortex increases trafficking of NR2A 
      subunits into spines, postsynaptic densities, and axon terminals.
PG  - 139-49
AB  - Past in vitro studies have used immunofluorescence to show increased clustering 
      of the NR1 subunits of NMDA receptors (NMDAR) following NMDAR blockade, 
      indicating that NMDARs self-regulate trafficking to and from spines. However, 
      since a substantial portion of spinous NMDAR subunits can reside at sites removed 
      from plasma membranes, whether or not these immunofluorescent clusters are 
      synaptic remains to be shown. Also, the NR2A/B subunits undergo 
      activity-dependent switching at synapses, indicating that their subcellular 
      distribution may be regulated differently from the NR1 subunits. We examined the 
      issue of NMDAR autoregulation by determining whether in vivo NMDAR blockade 
      enhances trafficking of the NR2A subunits toward spines and more specifically to 
      postsynaptic densities (PSDs) of already mature synapses. Seven adult rats 
      received unilateral intra-cortical infusion of the NMDAR antagonist, D-AP5 for 
      1/2-2 h and the inactive enantiomer or the solvent, alone, in the contralateral 
      cortex. Using an electron microscope, approximately 5600 cortical spines 
      originating from the two hemispheres of the seven adult animals were analyzed for 
      the location of NR2A subunits. In six out of the seven cases analyzed, the 
      D-AP5-treated neuropil exhibited increased immunolabeling at PSDs and a 
      concomitantly great increase at non-synaptic sites within spines. NR2A subunits 
      also increased presynaptically within 1/2 h but not after 1 h. These findings 
      indicate that NR2A subunits in intact, adult cortical neurons are prompted to 
      become trafficked into spines and axon terminals by NMDAR inactivity, yielding an 
      increase of a readily available reserve pool and greater localization at both 
      sides of synapses.
FAU - Aoki, Chiye
AU  - Aoki C
AD  - Center for Neural Science, New York University, Rm 809, 4 Washington Pl., New 
      York, NY 10003, USA. chiye@cns.nyu.edu
FAU - Fujisawa, Sho
AU  - Fujisawa S
FAU - Mahadomrongkul, Veera
AU  - Mahadomrongkul V
FAU - Shah, Priti J
AU  - Shah PJ
FAU - Nader, Karim
AU  - Nader K
FAU - Erisir, Alev
AU  - Erisir A
LA  - eng
GR  - R01 EY012138-04/EY/NEI NIH HHS/United States
GR  - R01-EY12138/EY/NEI NIH HHS/United States
GR  - R01-EY13145/EY/NEI NIH HHS/United States
GR  - 1 P30 EY13079/EY/NEI NIH HHS/United States
GR  - R01 EY012138/EY/NEI NIH HHS/United States
GR  - R01-NS 41091/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (NR2A NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - Anesthesia
MH  - Animals
MH  - Cerebral Cortex/*cytology/*drug effects
MH  - Dendrites/*drug effects
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Immunohistochemistry
MH  - Neuropil/drug effects
MH  - Presynaptic Terminals/*drug effects
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Synapses/*drug effects
EDAT- 2003/02/01 04:00
MHDA- 2003/04/29 05:00
CRDT- 2003/02/01 04:00
PHST- 2003/02/01 04:00 [pubmed]
PHST- 2003/04/29 05:00 [medline]
PHST- 2003/02/01 04:00 [entrez]
AID - S0006899302039628 [pii]
AID - 10.1016/s0006-8993(02)03962-8 [doi]
PST - ppublish
SO  - Brain Res. 2003 Feb 14;963(1-2):139-49. doi: 10.1016/s0006-8993(02)03962-8.