OSA's Digital Library

Journal of the Optical Society of America A

Journal of the Optical Society of America A


  • Editor: Franco Gori
  • Vol. 31, Iss. 4 — Apr. 1, 2014
  • pp: A189–A194

Specialized synaptic pathway for chromatic signals beneath S-cone photoreceptors is common to human, Old and New World primates

Christian Puller, Michael B. Manookin, Maureen Neitz, and Jay Neitz  »View Author Affiliations

JOSA A, Vol. 31, Issue 4, pp. A189-A194 (2014)

View Full Text Article

Enhanced HTML    Acrobat PDF (387 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



The distribution of the soluble NSF-attachment protein receptor protein syntaxin-4 and the Na-K-Cl cotransporter (NKCC) were investigated in the outer plexiform layer of human retina using immunohistochemistry. Both proteins, which are proposed to be components of a gamma-aminobutyric acid mediated feed-forward circuit from horizontal cells directly to bipolar cells, were enriched beneath S-cones. The expression pattern of syntaxin-4 was further analyzed in baboon and marmoset to determine if the synaptic specialization is common to primates. Syntaxin-4 was enriched beneath S-cones in both species, which together with the human results indicates that this specialization may have evolved for the purpose of mediating unique color vision capacities that are exclusive to primates.

© 2014 Optical Society of America

OCIS Codes
(330.0330) Vision, color, and visual optics : Vision, color, and visual optics
(330.1720) Vision, color, and visual optics : Color vision

ToC Category:
Retinal and cortical color processing

Original Manuscript: October 9, 2013
Manuscript Accepted: November 18, 2013
Published: February 12, 2014

Virtual Issues
Vol. 9, Iss. 6 Virtual Journal for Biomedical Optics

Christian Puller, Michael B. Manookin, Maureen Neitz, and Jay Neitz, "Specialized synaptic pathway for chromatic signals beneath S-cone photoreceptors is common to human, Old and New World primates," J. Opt. Soc. Am. A 31, A189-A194 (2014)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. C. Puller, S. Haverkamp, M. Neitz, and J. Neitz, “Synaptic elements for GABAergic feed-forward signaling between HII horizontal cells and blue cone bipolar cells are enriched beneath primate S-cones,” PloS 1 (to be published).
  2. C. Puller, M. B. Manookin, M. Neitz, and J. Neitz, “Syntaxin-4 is highly enriched beneath S-cone pedicles in the primate retina,” ARVO Meeting Abstracts 53, 6323 (2012).
  3. A. A. Hirano, J. H. Brandstatter, A. Vila, and N. C. Brecha, “Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes,” Vis. Neurosci. 24, 489–502 (2007). [CrossRef]
  4. D. M. Sherry, R. Mitchell, K. M. Standifer, and B. du Plessis, “Distribution of plasma membrane-associated syntaxins 1 through 4 indicates distinct trafficking functions in the synaptic layers of the mouse retina,” BMC Neurosci. 7, 54 (2006).
  5. H. Lee and N. C. Brecha, “Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells,” Eur. J. Neurosci. 31, 1388–1401 (2010). [CrossRef]
  6. J. Duebel, S. Haverkamp, W. Schleich, G. Feng, G. J. Augustine, T. Kuner, and T. Euler, “Two-photon imaging reveals somatodendritic chloride gradient in retinal ON-type bipolar cells expressing the biosensor clomeleon,” Neuron 49, 81–94 (2006). [CrossRef]
  7. N. Vardi, L. L. Zhang, J. A. Payne, and P. Sterling, “Evidence that different cation chloride cotransporters in retinal neurons allow opposite responses to GABA,” J. Neurosci. 20, 7657–7663 (2000).
  8. L. Peichl, “Morphology of interneurons: horizontal cells,” in Encyclopedia of the Eye, D. A. Dart, ed. (Academic, 2010), Vol. 3.
  9. H. Wässle, D. M. Dacey, T. Haun, S. Haverkamp, U. Grünert, and B. B. Boycott, “The mosaic of horizontal cells in the macaque monkey retina: with a comment on biplexiform ganglion cells,” Vis. Neurosci. 17, 591–608 (2000). [CrossRef]
  10. H. Wässle, B. B. Boycott, and J. Röhrenbeck, “Horizontal cells in the monkey retina: cone connections and dendritic network,” Eur. J. Neurosci. 1, 421–435 (1989). [CrossRef]
  11. P. Ahnelt and H. Kolb, “Horizontal cells and cone photoreceptors in primate retina: a golgi-light microscopic study of spectral connectivity,” J. Comp. Neurol. 343, 387–405 (1994). [CrossRef]
  12. P. Ahnelt and H. Kolb, “Horizontal cells and cone photoreceptors in human retina: a golgi-electron microscopic study of spectral connectivity,” J. Comp. Neurol. 343, 406–427 (1994). [CrossRef]
  13. D. M. Dacey, B. B. Lee, D. K. Stafford, J. Pokorny, and V. C. Smith, “Horizontal cells of the primate retina: cone specificity without spectral opponency,” Science 271, 656–659 (1996). [CrossRef]
  14. A. K. Goodchild, T. L. Chan, and U. Grünert, “Horizontal cell connections with short-wavelength-sensitive cones in macaque monkey retina,” Vis. Neurosci. 13, 833–845 (1996). [CrossRef]
  15. T. L. Chan and U. Grünert, “Horizontal cell connections with short wavelength-sensitive cones in the retina: a comparison between New World and Old World primates,” J. Comp. Neurol. 393, 196–209 (1998). [CrossRef]
  16. H. Kolb, A. Mariani, and A. Gallego, “A second type of horizontal cell in the monkey retina,” J. Comp. Neurol. 189, 31–44 (1980). [CrossRef]
  17. J. D. Crook, M. B. Manookin, O. S. Packer, and D. M. Dacey, “Horizontal cell feedback without cone type-selective inhibition mediates “red-green” color opponency in midget ganglion cells of the primate retina,” J. Neurosci. 31, 1762–1772 (2011). [CrossRef]
  18. O. S. Packer, J. Verweij, P. H. Li, J. L. Schnapf, and D. M. Dacey, “Blue-yellow opponency in primate S cone photoreceptors,” J. Neurosci. 30, 568–572 (2010). [CrossRef]
  19. H. Hirasawa, M. Yamada, and A. Kaneko, “Acidification of the synaptic cleft of cone photoreceptor terminal controls the amount of transmitter release, thereby forming the receptive field surround in the vertebrate retina,” J. Phys. Sci. 62, 359–375 (2012).
  20. L. J. Klaassen, I. Fahrenfort, and M. Kamermans, “Connexin hemichannel mediated ephaptic inhibition in the retina,” Brain Res. 1487, 25–38 (2012). [CrossRef]
  21. C. Guo, A. A. Hirano, S. L. Stella, M. Bitzer, and N. C. Brecha, “Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD 65, and the GABA vesicular transporter,” J. Comp. Neurol. 518, 1647–1669 (2010). [CrossRef]
  22. A. Jellali, C. Stussi-Garaud, B. Gasnier, A. Rendon, J. A. Sahel, H. Dreyfus, and S. Picaud, “Cellular localization of the vesicular inhibitory amino acid transporter in the mouse and human retina,” J. Comp. Neurol. 449, 76–87 (2002). [CrossRef]
  23. Y. Kao, L. Lassova, T. Bar-Yehuda, R. Edwards, P. Sterling, and N. Vardi, “Evidence that certain retinal bipolar cells use both glutamate and GABA,” J. Comp. Neurol. 478, 207–218 (2004). [CrossRef]
  24. M. Kalloniatis, R. E. Marc, and R. F. Murry, “Amino acid signatures in the primate retina,” J. Neurosci. 16, 6807–6829 (1996).
  25. S. Haverkamp, U. Grünert, and H. Wässle, “The cone pedicle, a complex synapse in the retina,” Neuron 27, 85–95 (2000). [CrossRef]
  26. J. G. Cueva, S. Haverkamp, R. J. Reimer, R. Edwards, H. Wässle, and N. C. Brecha, “Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells,” J. Comp. Neurol. 445, 227–237 (2002). [CrossRef]
  27. A. A. Hirano, J. H. Brandstatter, C. W. Morgans, and N. C. Brecha, “SNAP25 expression in mammalian retinal horizontal cells,” J. Comp. Neurol. 519, 972–988 (2011). [CrossRef]
  28. S. Deniz, E. Wersinger, Y. Schwab, C. Mura, F. Erdelyi, G. Szabo, A. Rendon, J. A. Sahel, S. Picaud, and M. J. Roux, “Mammalian retinal horizontal cells are unconventional GABAergic neurons,” J. Neurochem. 116, 350–362 (2011). [CrossRef]
  29. R. Herrmann, S. J. Heflin, T. Hammond, B. Lee, J. Wang, R. R. Gainetdinov, M. G. Caron, E. D. Eggers, L. J. Frishman, M. A. McCall, and V. Y. Arshavsky, “Rod vision is controlled by dopamine-dependent sensitization of rod bipolar cells by GABA,” Neuron 72, 101–110 (2011). [CrossRef]
  30. H. Wässle and M. H. Chun, “GABA-like immunoreactivity in the cat retina: light microscopy,” J. Comp. Neurol. 279, 43–54 (1989). [CrossRef]
  31. E. Agardh, B. Ehinger, and J.-Y. Wu, “GABA and GAD-like immunoreactivity in the primate retina,” Histochemistry 86, 485–490 (1987). [CrossRef]
  32. U. Grünert and H. Wässle, “GABA-like immunoreactivity in the macaque monkey retina: a light and electron microscopic study,” J. Comp. Neurol. 297, 509–524 (1990). [CrossRef]
  33. J. E. Dowling, J. E. Brown, and D. Major, “Synapses of horizontal cells in rabbit and cat retinas,” Science 153, 1639–1641 (1966). [CrossRef]
  34. H. Kolb, “The organization of the outer plexiform layer in the retina of the cat: electron microscopic observations,” J. Neurocytol. 6, 131–153 (1977). [CrossRef]
  35. S. K. Fisher and B. B. Boycott, “Synaptic connections made by horizontal cells within the outer plexiform layer of the retina of the cat and the rabbit,” Proc. R. Soc. Lond. B Biol. Sci. 186, 317–331 (1974).
  36. N. Vardi and P. Sterling, “Subcellular localization of GABAA receptor on bipolar cells in macaque and human retina,” Vision Res 34, 1235–1246 (1994). [CrossRef]
  37. C. Varela, R. Blanco, and P. De la Villa, “Depolarizing effect of GABA in rod bipolar cells of the mouse retina,” Vis. Res. 45, 2659–2667 (2005). [CrossRef]
  38. A. J. Chaffiol, Y. Cao, M. Ishii, C. Ribelayga, and S. C. Mangel, “Light/dark adaptive regulation of GABAA receptor and NKCC expression and activity modulates direct, GABA-mediated horizontal cell signaling to ON-cone bipolar cells,” Investig. Ophthalmol. Vis. Sci. 53, 4306 (2012). [CrossRef]
  39. C. Lytle, J. C. Xu, D. Biemesderfer, and B. Forbush, “Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies,” Am. J. Physiol. 269, C1496–C1505 (1995).
  40. L. L. Zhang, M. E. Fina, and N. Vardi, “Regulation of KCC2 and NKCC during development: membrane insertion and differences between cell types,” J. Comp. Neurol. 499, 132–143 (2006). [CrossRef]
  41. L. L. Zhang, E. Delpire, and N. Vardi, “NKCC1 does not accumulate chloride in developing retinal neurons,” J. Neurophysiol. 98, 266–277 (2007). [CrossRef]
  42. B. Li, K. McKernan, and W. Shen, “Spatial and temporal distribution patterns of Na-K-2Cl cotransporter in adult and developing mouse retinas,” Vis. Neurosci. 25, 109–123 (2008). [CrossRef]
  43. C. Puller and S. Haverkamp, “Cell-type-specific localization of protocadherin beta16 at AMPA and AMPA/Kainate receptor-containing synapses in the primate retina,” J. Comp. Neurol. 519, 467–479 (2011). [CrossRef]
  44. C. Puller, K. Ondreka, and S. Haverkamp, “Bipolar cells of the ground squirrel retina,” J. Comp. Neurol. 519, 759–774 (2011). [CrossRef]
  45. M. A. Raven, N. C. Orton, H. Nassar, G. A. Williams, W. K. Stell, G. H. Jacobs, N. T. Bech-Hansen, and B. E. Reese, “Early afferent signaling in the outer plexiform layer regulates development of horizontal cell morphology,” J. Comp. Neurol. 506, 745–758 (2008). [CrossRef]
  46. J. Röhrenbeck, H. Wässle, and B. B. Boycott, “Horizontal cells in the monkey retina: immunocytochemical staining with antibodies against calcium binding proteins,” Eur. J. Neurosci. 1, 407–420 (1989). [CrossRef]
  47. C. Chiquet, O. Dkhissi-Benyahya, and H. Cooper, “Calcium-binding protein distribution in the retina of strepsirhine and haplorhine primates,” Brain Res. Bull. 68, 185–194 (2005). [CrossRef]
  48. L. Missotten, The Ultrastructure of the Human Retina (Editions Arscia, 1965).
  49. C. Puller, L. P. de Sevilla Müller, U. Janssen-Bienhold, and S. Haverkamp, “ZO-1 and the spatial organization of gap junctions and glutamate receptors in the outer plexiform layer of the mammalian retina,” J. Neurosci. 29, 6266–6275 (2009). [CrossRef]
  50. W. B. Thoreson and S. C. Mangel, “Lateral interactions in the outer retina,” Prog. Retinal Eye Res. 31, 407–441 (2012). [CrossRef]
  51. D. M. Dacey and B. B. Lee, “The “blue-on” opponent pathway in primate retina originates from a distinct bistratified ganglion cell type,” Nature 367, 731–735 (1994). [CrossRef]
  52. D. J. Calkins, Y. Tsukamoto, and P. Sterling, “Microcircuitry and mosaic of a blue-yellow ganglion cell in the primate retina,” J. Neurosci. 18, 3373–3385 (1998).
  53. K. K. Ghosh and U. Grünert, “Synaptic input to small bistratified (blue-ON) ganglion cells in the retina of a new world monkey, the marmoset Callithrix jacchus,” J. Comp. Neurol. 413, 417–428 (1999). [CrossRef]
  54. K. A. Percival, P. R. Jusuf, P. R. Martin, and U. Grünert, “Synaptic inputs onto small bistratified (blue-ON/yellow-OFF) ganglion cells in marmoset retina,” J. Comp. Neurol. 517, 655–669 (2009). [CrossRef]
  55. J. D. Crook, C. M. Davenport, B. B. Peterson, O. S. Packer, P. B. Detwiler, and D. M. Dacey, “Parallel ON and OFF cone bipolar inputs establish spatially coextensive receptive field structure of blue-yellow ganglion cells in primate retina,” J. Neurosci. 29, 8372–8387 (2009). [CrossRef]
  56. D. M. Dacey, “Morphology of a small-field bistratified ganglion cell type in the macaque and human retina,” Vis. Neurosci. 10, 1081–1098 (1993). [CrossRef]
  57. S. Chen and W. Li, “A color-coding amacrine cell may provide a blue-OFF signal in a mammalian retina,” Nat. Neurosci. 15, 954–956 (2012). [CrossRef]
  58. L. Chang, T. Breuninger, and T. Euler, “Chromatic coding from cone-type unselective circuits in the mouse retina,” Neuron 77, 559–571 (2013). [CrossRef]
  59. A. Sher and S. H. DeVries, “A non-canonical pathway for mammalian blue-green color vision,” Nat. Neurosci. 15, 952–953 (2012). [CrossRef]
  60. B. Ekesten and P. Gouras, “Cone inputs to murine striate cortex,” BMC Neurosci. 9, 113 (2008). [CrossRef]
  61. B. Ekesten and P. Gouras, “Cone and rod inputs to murine retinal ganglion cells: evidence of cone opsin specific channels,” Vis. Neurosci. 22, 893–903 (2005). [CrossRef]
  62. B. P. Schmidt, M. Neitz, and J. Neitz, “Neurobiological hypothesis of color appearance and hue perception,” J. Opt. Soc. Am. A 31, A195–A207 (2014).

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.


Fig. 1. Fig. 2. Fig. 3.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited