Pharmacology of the skate electroretinogram indicates independent ON and OFF bipolar cell pathways.

Abstract

Organization of afferent information into parallel ON and OFF pathways is a critical feature of the vertebrate visual system. All afferent visual information in the vertebrate retina reaches the inner plexiform layer (IPL) via bipolar cells. It is at the bipolar cell level that separation of ON and OFF information first appears for afferent information from cones. This may also hold true for the rod pathway of cold-blooded vertebrates, but not for mammals. The all-rod retina of the skate presents an opportunity to examine such pathways in a retina having but a single class of photoreceptor. Immunocytochemical evidence suggests that both ON and OFF bipolar cells are present in the skate retina. We examined the pharmacology of the skate electroretinogram (ERG) to test the hypothesis that independent ON and OFF bipolar cell pathways are functional as rod afferent pathways from outer to inner plexiform layer in the skate. 100 txM 2-amino-4-phosphonobutyric acid (APB) reversibly blocked the skate ERG b-wave. A small d-wave-like OFF component of the ERG revealed by DC recording of response to a prolonged (10 s) flash of light was reduced or blocked by 5 mM kynurenic acid (KYN). We found that addition of 200 txM picrotoxin to the Ringer's solution revealed prominent ON and OFF components of the skate ERG while reducing the c-wave. These ON and OFF components were reversibly blocked by 100 tzM APB and 5 mM KYN, respectively. Reversible block of the OFF component by KYN was also accomplished in the presence of 500 I~M ALmethyl-DL-aspartate. From these findings, we conclude that ON and OFF bipolar cells are likely to be functional as parallel afferent interplexiform pathways in the allrod retina of the skate.

Effects of picrotoxin on light adapted frog electroretinogram are not due entirely to its action in proximal retina

“…Thus, its action leads to a decreased relative sensitivity of the ERG ON and OFF responses irrespective of the site it takes place. This suggestion is in line with the results of Chappell and Rosenstein (1996), who argue that picrotoxin enhancing effect upon the ON and OFF components of the skate ERG, exerted in the distal retina, is especially pronounced over a range of intensities 1 or 2 log units above threshold. The stronger effect of GABA at the lower stimulus intensities may be due in part to the fact that the gain of cone -horizontal cell synapse is highest for dim light modulation around the background illumination (Normann & Perlman, 1979).…”

“…It is possible that the site of picrotoxin action in rod-mediated pathways differs from that in cone-mediated ones. However, Chappell and Rosenstein (1996), who work on all rod retina of skate, have found that NMDA does not alter picrotoxin enhancing effects on the ERG ON and OFF component and suggest that the observed effects are due to picrotoxin action in distal retina. Thus, the GABAergic rod pathways may also originate in distal retina.…”

“…All these results support the hypothesis that the effects of picrotoxin on the b-and d-waves are due primarily to its action in proximal retina. However, Chappell and Rosenstein (1996) have shown that the enhanced ON and OFF components of skate ERG recorded during picrotoxin treatment are not reduced during the subsequent application of 500 lM NMDA. They proposed that picrotoxin effect is due to release from inhibition at the distal dendrites of ON and OFF bipolar cells.…”

“…Although Bonaventure, Wioland, and Jardon (1986) did not find any effect of picrotoxin on the d-wave, other authors reported that picrotoxin enhances the amplitude and delays the time course of the d-wave (Arnarsson & Eysteinsson, 1997;Belcheva & Kupenova, 1980;Belcheva & Vitanova, 1974Kupenova et al, 1991Kupenova et al, , 1997Lewis et al, 2011;Popova, 1989Popova, , 2000Popova et al, 1986;Vitanova et al, 1997;Xu & Karwoski, 1995). Picrotoxin revealed a prominent OFF component in all rod retina of skate (Chappell & Rosenstein, 1996) and in dark adapted toad retina (Katz et al, 1991). Thus, it appears that both the ON and OFF responses in nonmammalian ERG are under inhibitory GABAergic influences mediated by ionotropic GABA receptors.…”

Modification of the Xenopus electroretinogram by actions of glycine in the proximal retina

“…2‐Amino‐4‐phosphonobutyric acid has been shown to act as a specific agonist on ON centre bipolar cells in several species ( Slaughter & Miller 1981) including Xenopus ( Stone et al . 1990 ), thus removing the light responses of these cells and ON responses of all third‐order neurones, leaving OFF responses intact, but removing selectively the b‐wave of the ERG ( Stockton & Slaughter 1989, Chappell & Rosenstein 1996). The d‐wave is at least partly generated by activity of hyperpolarizing bipolar cells, which should not be affected by APB ( Slaughter & Miller 1981).…”