Effects of pH buffering on horizontal and ganglion cell light responses in primate retina: evidence for the proton hypothesis of surround formation

J Neurosci. 2008 Jan 9;28(2):456-64. doi: 10.1523/JNEUROSCI.2735-07.2008.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Action Potentials / radiation effects
  • Animals
  • Buffers
  • Dose-Response Relationship, Drug
  • HEPES / pharmacology
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Light*
  • Macaca fascicularis
  • Macaca nemestrina
  • Photic Stimulation / methods
  • Protons*
  • Retina / cytology*
  • Retinal Ganglion Cells* / drug effects
  • Retinal Ganglion Cells* / physiology
  • Retinal Ganglion Cells* / radiation effects
  • Retinal Horizontal Cells* / drug effects
  • Retinal Horizontal Cells* / physiology
  • Retinal Horizontal Cells* / radiation effects
  • Vision, Ocular


  • Buffers
  • Protons