The network-selective actions of quinoxalines on the neurocircuitry operations of the rabbit retina.
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.
Department of Physiology, University of Minnesota, 435 Delaware Street, Minneapolis, MN 55455, USA. ethan.cohen@yale.edu
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D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009415:Nerve Net / Q000187:drug effects* / Q000528:radiation effects; D011810:Quinoxalines / Q000494:pharmacology*; D011817:Rabbits; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000528:radiation effects; D012160:Retina / Q000187:drug effects* / Q000528:radiation effects / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000528:radiation effects; D014795:Visual Pathways / Q000187:drug effects* / Q000528:radiation effects / Q000648:ultrastructure; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C056723:FG 9041; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid