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.
