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Cone synapses in macaque fovea: I. Two types of non-S cones are distinguished by numbers of contacts with OFF midget bipolar cells

  • STAN SCHEIN (a1) (a2) (a3), IVY TRAN NGO (a1), TERESA M. HUANG (a1), KARL KLUG (a2), PETER STERLING (a4) and STEVE HERR (a1)...


L and M cones, divided into two groups by absorption spectra, have not been distinguished by structure. Here, we report what may be such a difference. We reconstructed the synaptic terminals of 16 non-S cones and the dendritic arbors of their ON and OFF midget bipolar cells from high-magnification electron micrographs of serial thin sections of a small region of macaque fovea. Each cone terminal contacted a similar number (~16) of invaginating central elements provided by its ON midget bipolar cell. By contrast, the numbers of connections between a cone terminal and its OFF midget bipolar cell were grouped into two clusters: 30–37 versus 43–50 basal contacts in the triad-associated position and 41–47 versus 61–74 Outer Densities within those basal contacts. The coefficients of variation of these distributions were all in the range of 10% or lower, characteristic of single populations. If these two clusters correspond to M- and L-cone circuits, the results reveal structural differences between M and L cones and between their corresponding OFF midget bipolar cells.


Corresponding author

*Address correspondence and reprint requests to: Stan Schein, Department of Psychology, Franz Hall, Mailcode 951563, University of California, Los Angeles, Los Angeles, CA 90095-1563. E-mail:


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Ahmad, K.M., Klug, K., Herr, S., Sterling, P. & Schein, S. (2003). Cell density ratios in a foveal patch in macaque retina. Visual Neuroscience 20, 189209.
Ahnelt, P.K., Keri, C. & Kolb, H. (1990). Identification of terminals of putative blue-sensitive cones in human and primate retina. The Journal of Comparative Neurology 293, 3953.
Ahnelt, P.K., Kolb, H. & Pflug, R. (1987). Identification of subtype of cone photoreceptor, likely to be blue sensitive, in the human retina. The Journal of Comparative Neurology 255, 1834.
Bowmaker, J.K., Parry, J.W.L. & Mollon, J.D. (2003). The arrangement of L and M cones in human and a primate retina. In Normal and Defective Colour Vision, ed. Mollon, J.D., Pokorny, J. & Knoblauch, K., pp. 3950. Oxford: Oxford University Press.
Boycott, B.B. & Dowling, J.E. (1969). Organization of the primate retina: Light microscopy. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 255, 109176.
Boycott, B.B. & Hopkins, J.M. (1991). Cone bipolar cells and cone synapses in the primate retina. Visual Neuroscience 7, 4960.
Brainard, D.H., Roorda, A., Yamauchi, Y., Calderone, J.B., Metha, A., Neitz, M., Neitz, J., Williams, D.R. & Jacobs, G.H. (2000). Functional consequences of the relative numbers of L and M cones. Journal of the Optical Society of America A, Optics, Image Science, and Vision 17, 607614.
Calkins, D. (1994). Microcircuitry of M and L Cone Midget Ganglion Cell Pathways in the Primate Fovea. PhD thesis, Philadelphia, PA: University of Pennsylvania.
Calkins, D., Schein, S., Tsukamoto, Y. & Sterling, P. (1994). M and L cones in macaque fovea connect to midget ganglion cells by different numbers of excitatory synapses. Nature 371, 7072.
Calkins, D. & Sterling, P. (2007). Microcircuitry for two types of achromatic ganglion cell in primate fovea. The Journal of Neuroscience 27, 26462653.
Carroll, J., Neitz, M. & Neitz, J. (2002). Estimates of L:M cone ratio from ERG flicker photometry and genetics. Journal of Vision 2, 531542.
Chun, M., Grünert, U., Martin, P. & Wässle, H. (1996). The synaptic complex of cones in the fovea and in the periphery of the macaque monkey retina. Vision Research 36, 33733381.
Cicerone, C.M. & Nerger, J.L. (1989). The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis. Vision Research 29, 115128.
Cohen, E. & Sterling, P. (1990) Demonstration of cell types among cone bipolar neurons of cat retina. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 330, 305321.
Cohen, E. & Sterling, P. (1992). Parallel circuits from cones to the on-beta ganglion cell. The European Journal of Neuroscience 4, 506520.
Deeb, S.S., Diller, L.C., Williams, D.R. & Dacey, D.M. (2000). Interindividual and topographical variation in L:M cone ratios in monkey retinas. Journal of the Optical Society of America A, Optics, Image Science, and Vision 17, 538544.
Dobkins, K.R., Thiele, A. & Albright, T.D. (2000). Comparison of red-green equiluminance points in humans and macaques: Evidence for different L:M cone ratios between species. Journal of the Optical Society of America A, Optics, Image Science, and Vision 17, 545556.
Dowling, J.E. (1987). The Retina: An Approachable Part of the Brain. Cambridge, MA: Harvard University Press.
Dowling, J.E. & Boycott, B.B. (1966). Organization of the primate retina: Electron microscopy. Proceedings of the Royal Society of London. Series B, Biological Sciences 166, 80111.
Eggers, G., Sterling, P. & Schein, S. (1999). Midget bipolar cells makes three types of membrane density with midget ganglion cells. Investigative Ophthalmology & Visual Science 40, S813.
Eriköz, B., Jusuf, P.R., Percival, K.A. & Grünert, U. (2008). Distribution of bipolar input to midget and parasol ganglion cells in marmoset retina. Visual Neuroscience 25, 6776.
Hagstrom, S.A., Neitz, J. & Neitz, M. (1998). Variations in cone populations for red-green color vision examined by analysis of mRNA. Neuroreport 9, 19631967.
Hartigan, J.A. & Hartigan, P.M. (1985). The dip test of unimodality. Annals of Statistics 13, 7084.
Haverkamp, S., Grünert, U. & Wässle, H. (2001). The synaptic architecture of AMPA receptors at the cone pedicle of the primate retina. The Journal of Neuroscience 21, 24882500.
Hering, E. (1878). Zur Lehre von Lichtsinne. Vienna, Austria: C. Gerold’s Sohn.
Hering, E. (1920). Outlines of a Theory of the Light Sense, trans. Hurvich, L.M. & Jameson, D. (1964). Cambridge, MA: Harvard University Press.
Herr, S., Klug, K., Sterling, P. & Schein, S. (2003). Inner S-cone bipolar cells provide all of the central elements for S cones in macaque retina. The Journal of Comparative Neurology 457, 185201.
Herr, S., Ngo, I.T., Huang, T.M., Klug, K., Sterling, P. & Schein, S. (2011). Cone synapses in macaque fovea: II. Dendrites of OFF midget bipolar cells exhibit Inner Densities similar to their outer synaptic densities in basal contacts with cone terminals. Visual Neuroscience, 28, xxxxxx.
Hofer, H., Carroll, J., Neitz, J., Neitz, M. & Williams, D.R. (2005). Organization of the human trichromatic cone mosaic. The Journal of Neuroscience 25, 96699679.
Hopkins, J.M. & Boycott, B.B. (1992). Synaptic contacts of a two-cone flat bipolar cell in a primate retina. Visual Neuroscience 8, 379384.
Hopkins, J.M. & Boycott, B.B. (1997). The cone synapses of cone bipolar cells of primate retina. Journal of Neurocytology 26, 313325.
Hurvich, L. & Jameson, D. (1957). An opponent-process theory of color vision. Psychological Review 64, 384404.
Jacobs, G.H. & Deegan, J.F. II (1997). Spectral sensitivity of macaque monkeys measured with ERG flicker photometry. Visual Neuroscience 14, 921928.
Jusuf, P.R., Martin, P.R. & Grünert, U. (2006). Synaptic connectivity in the midget-parvocellular pathway of primate central retina. The Journal of Comparative Neurology 494, 260274.
Klug, K., Herr, S., Ngo, I.T., Sterling, P. & Schein, S. (2003). Macaque retina contains an S-cone OFF midget pathway. The Journal of Neuroscience 23, 98819887.
Kolb, H. (1970). Organization of the outer plexiform layer of the primate retina: Electron microscopy of Golgi-impregnated cells. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences 258, 261283.
Kolb, H., Boycott, B.B. & Dowling, J.E. (1969). A second type of midget bipolar cell in the primate retina. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 255, 177184.
Kolb, H., Linberg, K.A. & Fisher, S.K. (1992). Neurons of the human retina: A Golgi study. The Journal of Comparative Neurology 318, 146187.
Kuchenbecker, J.A., Sahay, M., Tait, D.M., Neitz, M. & Neitz, J. (2008). Topography of the long- to middle-wavelength sensitive cone ratio in the human retina assessed with a wide-field color multifocal electroretinogram. Visual Neuroscience 25, 301306.
Lerea, C.L., Bunt-Milam, A.H. & Hurley, B. (1989). Alpha transducin is present in blue-, green-, and red-sensitive cone photoreceptors in the human retina. Neuron 3, 367376.
Mechler, F. & Ringach, D.L. (2002). On the classification of simple and complex cells. Vision Research 42, 10171033.
Meyers, D., Skinner, S. & Sloan, K. (1992). Surfaces from contours. ACM Transactions on Graphics 11, 228258.
Missotten, L. (1965). The Ultrastructure of the Human Retina. Brussels, Belgium: Editions Arscia S.A.
Milam, A.H., Dacey, D.M. & Dizhoor, A.M. (1993). Recoverin immunoreactivity in mammalian cone bipolar cells. Visual Neuroscience 10, 112.
Mollon, J.D. & Bowmaker, J.K. (1992). The spatial arrangement of cones in the primate fovea. Nature 360, 677679.
Neitz, M., Balding, S.D., McMahon, C., Sjoberg, S.A. & Neitz, J. (2006). Topography of long- and middle-wavelength sensitive cone opsin gene expression in human and Old World monkey retina. Visual Neuroscience 23, 379385.
Nomura, A., Shigemoto, R., Nakamura, Y., Okamoto, N., Mizuno, N. & Nakanishi, S. (1994). Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Cell 77, 361369.
Otake, S. & Cicerone, C. (2000). L and M cone relative numerosity and red-green opponency from fovea to mid-periphery in the human retina. Journal of the Optical Society of America A, Optics, Image Science, and Vision 17, 615627.
Packer, O.S., Williams, D.R. & Bensinger, D.G. (1996). Photopigment transmittance imaging of the primate photoreceptor mosaic. The Journal of Neuroscience 16, 22512260.
Polyak, S.L. (1941). The Retina. Chicago, IL: University of Chicago Press.
Raviola, E. & Gilula, N.B. (1975). Intramembrane organization of specialized contacts in the outer plexiform layer of the retina. A freeze-fracture study in monkeys and rabbits. The Journal of Cell Biology 65, 192222.
Rodieck, R.W. (1991). Which cells code for color? In From Pigments to Perception: Advances in Understanding Visual Elements, ed. Valberg, A. & Lee, B.B., pp. 8389. New York: Plenum.
Roorda, A., Mehta, A.B., Lennie, P. & Williams, D.A. (2001). Packing arrangement of the three cone classes in the primate retina. Vision Research 41, 12911306.
Roorda, A. & Williams, D.A. (1999). The arrangement of the three cone classes in the human eye. Nature 397, 520522.
Schein, S.J. (1988). Anatomy of macaque fovea and spatial densities of neurons in foveal representation. The Journal of Comparative Neurology 269, 479505.
Shevell, S.K. & Humanski, R.A. (1988). Color perception under chromatic adaptation: Red/green equilibria with adapted short-wavelength-sensitive cones. Vision Research 12, 13451356.
Shinomori, K., Spillmann, L. & Werner, J.S. (1999). S-cone signals to temporal OFF-channels: Asymmetrical connections to postreceptoral chromatic mechanisms. Vision Research 39, 3949.
Smith, R.G. (1987). Montage: A system for three-dimensional reconstruction by personal computer. Journal of Neuroscience Methods 21, 5569.
Szél, A., Diamantstein, T. & Rohlich, P. (1988). Identification of the blue-sensitive cones in the mammalian retina by anti-visual pigment antibody. The Journal of Comparative Neurology 273, 593602.
Tan, P.-N., Steinbach, M. & Kumar, V. (2006). Introduction to Data Mining. Harlow, UK: Addison-Wesley Longman.
Telkes, I., Lee, S.C.S., Jusuf, P.R. & Grünert, U. (2008). The midget-parvocellular pathway of marmoset retina: A quantitative light microscopic study. The Journal of Comparative Neurology 510, 539549.
Tsukamoto, Y., Masarachia, P., Schein, S. & Sterling, P. (1992). Gap junctions between the terminals of macaque foveal cones. Vision Research 32, 18091815.
Vardi, N., Duvoisin, R., Wu, G. & Sterling, P. (2000). Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. The Journal of Comparative Neurology 423, 402412.
Vardi, N., Morigiwa, K., Wang, T.L., Shi, Y.J. & Sterling, P. (1998). Neurochemistry of the mammalian cone ‘synaptic complex’. Vision Research 38, 13591369.
Wässle, H., Grünert, U., Martin, P.R. & Boycott, B.B. (1994). Immunocytochemical characterization and spatial distribution of midget bipolar cells in the macaque monkey retina. Vision Research 34, 561579.
Wooten, B.R. & Werner, J.S. (1979). Short-wave cone input to the red-green opponent channel. Vision Research 19, 10531054.
Wuerger, S.M., Atkinson, P. & Cropper, S. (2005) The cone inputs to the unique-hue mechanisms. Vision Research 45, 32103223.



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