Abstract
A fundamental feature of the visual system is its ability to detect image contrast. The contrast processing starts in the first synapse of the retina where parallel pathways are established to compute contrast to bright (ON pathway) and dark (OFF pathway) objects, separately transferred to morphologically identified ON and OFF cells throughout the visual system. Here, we found that response polarity in ON and OFF neurons is not fixed but rather switches dynamically to the opposite polarity. The switch was not observed in rod-knockout mice, indicating that rods generate the polarity switch. We determined that neither horizontal cells nor rod-signaling pathways were responsible for the switch. Instead, we discovered that EAAT5 glutamate transporters located at photoreceptor terminals were required to produce the polarity switch. Our findings exhibit the plasticity of ON-OFF coding in retinal interneurons and their ability to encode contrast across the visual dynamic range.
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Supplementary Data 1 includes all source data and is provided with this paper. Any additional data are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank Drs. Dao-Qi Zhang and Samar Hattar for providing photoreceptor KO mice. The authors also thank Dr. Manoranjan Santra for genotyping support and Mr. Bashir Khatib-Shahidi and Mr. Goichi Suganuma for technical assistance. The authors are grateful to generous research funding: NIH EY028915 (T.I.), NIH EY032917 (T.I.), NIH EY004068 (Vision Core), Rumble Fellowship (J.M.B.), and RPB grant.
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C.B.H. and T.I. were responsible for conceptualizing the study. D.L.B., A.R.H., A.S., J.M.B., and C.B.H. performed a patch clamp study and analyzed data. D.L.B. and S.K performed statistical analysis. Y.U. and E.C.S. advised on light adaptations and provided photoreceptor mutant mouse analysis. T.I. wrote the original manuscript. D.L.B., A.R.H., A.S., and C.B.H. generated figures. All authors reviewed and edited the manuscript.
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Beaudoin, D.L., Hassan, A.R., Shehu, A. et al. Rod photoreceptors control the ON vs OFF polarity of cone-signaling neurons. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09885-4
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DOI: https://doi.org/10.1038/s42003-026-09885-4
