WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, November 5, 2008, 28(45):11685-11694; doi:10.1523/JNEUROSCI.3035-08.2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harney, S. C.
Right arrow Articles by Anwyl, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harney, S. C.
Right arrow Articles by Anwyl, R.

 Previous Article  |  Next Article 

Cellular/Molecular
Extrasynaptic NR2D-Containing NMDARs Are Recruited to the Synapse during LTP of NMDAR-EPSCs

Sarah C. Harney,1 David E. Jane,2 and Roger Anwyl1

1Department of Physiology, Trinity College, Dublin 2, Ireland, and 2Department of Pharmacology, Medical Research Council Centre for Synaptic Plasticity, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom

Correspondence should be addressed to Roger Anwyl, Department of Physiology, Trinity College, Dublin 2, Ireland. Email: ranwyl{at}tcd.ie

Long-term potentiation of NMDA-receptor-mediated synaptic transmission (NMDAR-LTP) is a little-understood form of plasticity. In the present study, we investigated whether NMDAR-LTP in the dentate gyrus involves recruitment of extrasynaptic NMDARs, because NMDARs are expressed both synaptically and extrasynaptically with evidence for subtype differences at different locations. We show that before induction of NMDAR-LTP, pharmacological inhibition of glutamate transporters resulted in glutamate spillover from the synapse and activation of extrasynaptic NMDARs. After the induction of NMDAR-LTP, such activation of extrasynaptic NMDARs was absent. Activation of extrasynaptic NMDARs after glutamate uptake inhibition also occurred when synaptic NMDARs were inhibited with MK801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], and this extrasynaptically mediated NMDAR-EPSC was strongly reduced by prior induction of NMDAR-LTP. The extrasynaptic NMDARs were shown to be NR2D-containing, because the activation of extrasynaptic NMDARs by glutamate spillover was prevented by the NR2D-selective antagonists PPDA [(2R*,3S*)-1-(phenanthrenyl-2-carbonyl)piperazine-2,3-dicarboxylic acid] and UBP141. Further studies using selective antagonists for NR2A- and NR2B-containing NMDARs demonstrated that synaptic NMDARs are predominantly NR2A-containing and NR2B-containing receptors, whereas the extrasynaptic NMDARs are complex multimeric receptors with NR2A, NR2B, or NR2D subunits. Our results show that LTP of NMDAR-EPSCs involves movement of NMDARs from an extrasynaptic to a synaptic location and suggest a novel physiological role for extrasynaptic NMDARs.

Key words: NMDA receptor; synaptic plasticity; LTP; dentate gyrus; glutamate transporters; patch clamp

Received June 27, 2008; revised Sept. 10, 2008; accepted Sept. 20, 2008.

Correspondence should be addressed to Roger Anwyl, Department of Physiology, Trinity College, Dublin 2, Ireland. Email: ranwyl{at}tcd.ie






 -
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-