Effects of pH Buffering on Horizontal and Ganglion Cell Light Responses in Primate Retina: Evidence for the Proton Hypothesis of Surround Formation

Abstract

Negative feedback from horizontal cells to cone photoreceptors is regarded as the critical pathway for the formation of the antagonistic surround of retinal neurons, yet the mechanism by which horizontal cells accomplish negative feedback has been difficult to determine. Recent evidence suggests that feedback uses a novel, non-GABAergic pathway that directly modulates the calcium current in cones. In non-mammalian vertebrates, enrichment of retinal pH buffering capacity attenuates horizontal cell feedback, supporting one model in which feedback occurs by horizontal cell modulation of the extracellular pH in the cone synaptic cleft. Here we test the effect of exogenous pH buffering on the response dynamics of H1 horizontal cells and the center-surround receptive field structure of parasol ganglion cells in the macaque monkey retina. Enrichment of the extracellular buffering capacity with HEPES selectively attenuates surround antagonism in parasol ganglion cells. The H1 horizontal cell light response includes a slow, depolarizing component that is attributed to negative feedback to cones. This part of the response is attenuated by HEPES and other pH buffers in a dose-dependent manner that is correlated with predicted buffering capacity. The selective effects of pH buffering on the parasol cell surround and H1 cell light response suggests that, in primate retina, horizontal cell feedback to cones is mediated via a pH-dependent mechanism and is a major determinant of the ganglion cell receptive field surround.

Three Distinct Blue-Green Color Pathways in a Mammalian Retina

“…intermediary amacrine cell; spiking in this squirrel SϪ/Mϩ ganglion cell was also blocked by L-AP4 (Chen and Li, 2012;Sher and DeVries, 2012). We call this cell the "inverted S-OFF" because the polarity is the inversion of the S-ON bipolar cell.…”

“…Blue (B) and green (G) LEDs provided full-field chromatic stimuli and were positioned 80 mm from the chamber. Cone-isolating stimuli were constructed by measuring the spectral composition of the LEDs and using the absorption spectra of rabbit M-cone and S-cones to balance the B-LED and G-LED outputs to produce stimulus transitions that strongly activated one cone type while leaving cone capture unchanged in the other cone type (Estévez and Spekreijse, 1982;Crook et al, 2009). Spectral intensities were measured with an ILT1700 radiometer (International Light Technologies).…”

“…Color opponent cells combine an OFF response to one hue with an ON response to another hue; for example, S-ON and M-OFF (Crook et al, 2009;Yin et al, 2009). Responses are maximal when the opponent hues are presented out of phase, so that the ON response to one hue will combine with the OFF response to the other hue.…”

“…The canonical circuit for color opponency consists of a receptive field center response generated by an ON or OFF type bipolar cell with selective S-cone or M-cone input and an antagonistic surround produced by feedback from horizontal cells to the cone photoreceptor terminals (Crook et al, 2009;Packer et al, 2010). Rabbit horizontal cells contact cones nonselectively (Hack and Peichl, 1999); therefore, the preponderance of M-cones over S-cones provides strong M antagonism of S-cones.…”

“…However, an M-center/S-surround would be difficult to produce with M-dominated horizontal cells and although OFF blue cone bipolar cells have been reported in primate and rabbit retinas (Klug et al, 2003;Liu and Chiao, 2007), this pathway has remained controversial and has yet to be demonstrated by physiological techniques. Two recent reports in ground squirrel retina were able to circumvent this difficulty by providing evidence for an SϪ/Mϩ pathway derived via inversion of the canonical Sϩ/MϪ signal by an intervening amacrine cell (Chen and Li, 2012;Sher and DeVries, 2012).…”