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Localization of NMDA receptor subunits and mapping NMDA drive within the mammalian retina

Published online by Cambridge University Press:  01 July 2004

MICHAEL KALLONIATIS ,
DANIEL SUN ,
LISA FOSTER ,
SILKE HAVERKAMP  and
HEINZ WÄSSLE
MICHAEL KALLONIATIS
Affiliation:
Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia
DANIEL SUN
Affiliation:
Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand
LISA FOSTER
Affiliation:
Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia
SILKE HAVERKAMP
Affiliation:
Max-Planck-Insitut für Hirnforschung, Frankfurt/M, Germany
HEINZ WÄSSLE
Affiliation:
Max-Planck-Insitut für Hirnforschung, Frankfurt/M, Germany
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Abstract

Glutamate is a major neurotransmitter in the retina and other parts of the central nervous system, exerting its influence through ionotropic and metabotropic receptors. One ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor, is central to neural shaping, but also plays a major role during neuronal development and in disease processes. We studied the distribution pattern of different subunits of the NMDA receptor within the rat retina including quantifying the pattern of labelling for all the NR1 splice variants, the NR2A and NR2B subunits. The labelling pattern for the subunits was confined predominantly in the outer two-thirds of the inner plexiform layer. We also wanted to probe NMDA receptor function using an organic cation, agmatine (AGB); a marker for cation channel activity. Although there was an NMDA concentration-dependent increase in AGB labelling of amacrine cells and ganglion cells, we found no evidence of functional NMDA receptors on horizontal cells in the peripheral rabbit retina, nor in the visual streak where the type A horizontal cell was identified by GABA labelling. Basal AGB labelling within depolarizing bipolar cells was also noted. This basal bipolar cell AGB labelling was not modulated by NMDA and was completely abolished by the use of L-2-amino-4-phosphono-butyric acid, which is known to hyperpolarize retinal depolarizing bipolar cells. AGB is therefore not only useful as a probe of ligand-gated drive, but can also identify neurons that have constitutively open cationic channels. In combination, the NMDA receptor subunit distribution pattern and the AGB gating experiments strongly suggests that this ionotropic glutamate receptor is functional in the cone-driven pathway of the inner retina.

Keywords

GlutamateNR1NR1C2NR1C2′NR2ANR2BAgmatine; L-AP4
Type
Research Article
Information
Visual Neuroscience , Volume 21 , Issue 4 , July 2004 , pp. 587 - 597
Copyright
2004 Cambridge University Press

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