HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 586/3/739    most recent jphysiol.2007.144618v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Brothwell, S. L. C. Articles by Jones, S. PubMed PubMed Citation Articles by Brothwell, S. L. C. Articles by Jones, S. Related Collections Neuroscience

¹ Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
² Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha
³ Department of Physiology and Pharmacology, MRC Centre for Synaptic Plasticity, University of Bristol, Bristol, UK
⁴ Department of Pharmacology, University College London, London, UK

NMDA receptors are present at glutamatergic synapses throughout the brain, and are important for the development and plasticity of neural circuits. Their subunit composition is developmentally regulated. We have investigated the developmental profile of functional synaptic NMDA receptor subunits in dopaminergic neurones of the substantia nigra pars compacta (SNc). In SNc dopaminergic neurones from rats aged postnatal day (P)7, ifenprodil inhibited NMDA-EPSCs with an estimated IC₅₀ of 0.36 µM and a maximum inhibition of 73.5 ± 2.7% (10 µM), consistent with a substantial population of NR1/NR2B-containing diheteromeric receptors. UBP141, a novel NR2D-preferring antagonist, inhibited NMDA-EPSCs with an estimated IC₅₀ of 6.2 µM. During postnatal development, the maximum inhibitory effect of 10 µM ifenprodil significantly decreased. However, NMDA-EPSCs were not inhibited by Zn²⁺ (200 nM) or potentiated by the Zn²⁺ chelator TPEN (1 µM), and the effect of UBP141 did not increase during development, indicating that NR2B subunits are not replaced with diheteromeric NR2A or NR2D subunits. The time course of the decay of NMDA-EPSCs was not significantly changed in ifenprodil at any age tested. Together, these data suggest that diheteromeric NR1/NR2A or NR1/NR2D receptors do not account for the ifenprodil-resistant component of the NMDA-EPSC. We propose that NR1/NR2B/NR2D triheteromers form a significant fraction of synaptic NMDA receptors during postnatal development. This is the first report of data suggesting NR2D-containing triheteromeric NMDA receptors at a brain synapse.

(Received 11 September 2007; accepted after revision 21 November 2007; first published online 22 November 2007)
Corresponding author S. Jones: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Email: sj251{at}cam.ac.uk

This article has been cited by other articles:

				D. J. A. Wyllie 2B or 2B and 2D? - That is the question J. Physiol., February 1, 2008; 586(3): 693 - 693. [Full Text] [PDF]