Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 2, Pages 456-464Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2735-07.2008
Keywords
retina; horizontal cell; ganglion cell; feedback; surround; proton
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Funding
- NCRR NIH HHS [RR00166, P51 RR000166] Funding Source: Medline
- NEI NIH HHS [EY01730, R01 EY002048, R01 EY002048-31, EY02048, R01 EY006678, P30 EY001730, EY06678] Funding Source: Medline
- NIGMS NIH HHS [GM07108, T32 GM007108] Funding Source: Medline
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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.
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