The network-selective actions of quinoxalines on the neurocircuitry operations of the rabbit retina.

Abstract

We examined the contribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxalole-4-propionic acid (AMPA)/kainate (KA) receptors to the light-responses of rabbit retinal neurons. In the outer retina, bath application of the AMPA/KA receptor antagonists 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and 2,3,dihydroxy-6-nitro-7-sulfamoyl-benzo-f-quinoxaline (NBQX) blocked the light-responses of horizontal cells. Application of quinoxalines enhanced ON-bipolar cell light-responses, and was associated with a hyperpolarization of their resting potentials. In the inner retina, application of both AMPA/KA and NMDA antagonists to AII amacrine-like cells only partially blocked their light-responses. Their residual responses may reflect electrical coupling to neighboring ON-center cone bipolar cells, and can inhibit OFF-center ganglion cells. ON-sustained ganglion cells were highly sensitive to the quinoxalines, which reduced their light-evoked firing, while the firing of ON-transient cells remained as NMDA-mediated light-responses. Quinoxalines had differential effects on the firing rates of ON- and OFF-center ganglion cells: ON-cells were reduced, while OFF-cells were increased. In contrast, firing rates of ON-OFF ganglion cells were not excited by NBQX, and showed a recovered light-response mediated by NMDA receptors. The receptive field surround was lost in ganglion cells. For comparison, NMDA antagonists had only moderate effects on all ganglion cell light-responses. Our results indicate that NMDA and AMPA/KA receptors both contribute to ganglion cell light-responses. However, AMPA/KA receptors also significantly effect the light-response of neurons presynaptic to retinal ganglion cells, altering the observed pharmacology at the ganglion cell level.

• Authors: E D Cohen, R F Miller
• Journal: Brain research (Brain Res) Vol. 831 Issue 1-2 Pg. 206-28 (Jun 12 1999) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10412000 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 1999 Elsevier Science B.V.

Chemical References

• Excitatory Amino Acid Antagonists
• Quinoxalines
• Receptors, Glutamate
• 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
• FG 9041
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Topics

• Animals
• Excitatory Amino Acid Antagonists (pharmacology)
• Light
• Membrane Potentials (drug effects, radiation effects)
• Nerve Net (drug effects, radiation effects)
• Quinoxalines (pharmacology)
• Rabbits
• Receptors, Glutamate (drug effects, radiation effects)
• Retina (drug effects, radiation effects, ultrastructure)
• Retinal Ganglion Cells (drug effects, radiation effects)
• Visual Pathways (drug effects, radiation effects, ultrastructure)
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (pharmacology)