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  • Review Article
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Retinal bipolar cells: elementary building blocks of vision

Key Points

  • Bipolar cells are the only neurons that connect the outer retina to the inner retina. They implement an 'extra' layer of processing that is not typically found in other sensory organs.

  • The different types (typically more than ten) of bipolar cells systematically transform the photoreceptor signal in different ways, most notably, but not exclusively, in terms of chromatic preference, polarity (ON versus OFF) and kinetics (transient versus sustained responses).

  • Bipolar cells first shape their specific response properties at their dendrites through a plethora of mechanisms involving different contact morphologies, receptor types and secondary messenger systems, as well as lateral inputs from horizontal cells.

  • Additional scope for signal modification exists in the axonal terminal system, in which local ionic currents and lateral inputs from amacrine cells contribute to shaping a bipolar cell's final output to its postsynaptic partners.

  • Individual bipolar cells may, in principle, provide differential input to different postsynaptic circuits.

  • Postsynaptic circuits may combine inputs from different types of bipolar cells to inherit different, highly specific signalling properties.

Abstract

Retinal bipolar cells are the first 'projection neurons' of the vertebrate visual system — all of the information needed for vision is relayed by this intraretinal connection. Each of the at least 13 distinct types of bipolar cells systematically transforms the photoreceptor input in a different way, thereby generating specific channels that encode stimulus properties, such as polarity, contrast, temporal profile and chromatic composition. As a result, bipolar cell output signals represent elementary 'building blocks' from which the microcircuits of the inner retina derive a feature-oriented description of the visual world.

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Figure 1: Organization of the bipolar cells in a mammalian retina.
Figure 2: Bipolar cell anatomy.
Figure 3: Shaping bipolar cell signals: dendrites and axon terminals.
Figure 4: Building ganglion cell circuits from bipolar cell elementary operations.

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References

  1. Dreosti, E., Odermatt, B., Dorostkar, M. M. & Lagnado, L. A genetically encoded reporter of synaptic activity in vivo. Nature Methods 6, 883–889 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Baden, T., Berens, P., Bethge, M. & Euler, T. Spikes in mammalian bipolar cells support temporal layering of the inner retina. Curr. Biol. 23, 48–52 (2013). A study in mice showing direct measurements of light-evoked presynaptic calcium responses in axonal terminals of bipolar cells that stratify at different depths within the IPL.

    Article  CAS  PubMed  Google Scholar 

  3. Yonehara, K. et al. The first stage of cardinal direction selectivity is localized to the dendrites of retinal ganglion cells. Neuron 79, 1078–1085 (2013). A mouse study demonstrating that direction selectivity is not a feature of bipolar cell output.

    Article  CAS  PubMed  Google Scholar 

  4. Marvin, J. S. et al. An optimized fluorescent probe for visualizing glutamate neurotransmission. Nature Methods 10, 162–170 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Borghuis, B. G., Marvin, J. S., Looger, L. L. & Demb, J. B. Two-photon imaging of nonlinear glutamate release dynamics at bipolar cell synapses in the mouse retina. J. Neurosci. 33, 10972–10985 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Helmstaedter, M. et al. Connectomic reconstruction of the inner plexiform layer in the mouse retina. Nature 500, 168–174 (2013). This paper provides a comprehensive, high-density electron microscopy-based reconstruction of a small patch of mouse retina.

    Article  CAS  PubMed  Google Scholar 

  7. Puthussery, T., Venkataramani, S., Gayet-Primo, J., Smith, R. G. & Taylor, W. R. NaV1.1 channels in axon initial segments of bipolar cells augment input to magnocellular visual pathways in the primate retina. J. Neurosci. 33, 16045–16059 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tartuferi, F. Sull'anatomia della retina. Int. Monatsschrift Anat.Physiol. 4, 421–441 (in Italian) (1887).

    Google Scholar 

  9. Lin, B. & Masland, R. H. Synaptic contacts between an identified type of ON cone bipolar cell and ganglion cells in the mouse retina. Eur. J. Neurosci. 21, 1257–1270 (2005).

    Article  PubMed  Google Scholar 

  10. Morgan, J. L., Soto, F., Wong, R. O. & Kerschensteiner, D. Development of cell type-specific connectivity patterns of converging excitatory axons in the retina. Neuron 71, 1014–1021 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Neumann, S. & Haverkamp, S. Characterization of small-field bistratified amacrine cells in macaque retina labeled by antibodies against synaptotagmin-2. J. Comp. Neurol. 521, 709–724 (2013).

    Article  CAS  PubMed  Google Scholar 

  12. Hartveit, E. Functional organization of cone bipolar cells in the rat retina. J. Neurophysiol. 77, 1716–1730 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. Wässle, H., Puller, C., Müller, F. & Haverkamp, S. Cone contacts, mosaics, and territories of bipolar cells in the mouse retina. J. Neurosci. 29, 106–117 (2009). Key work on the anatomical identification of bipolar cell types and their organization in the mouse.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Connaughton, V. P., Graham, D. & Nelson, R. Identification and morphological classification of horizontal, bipolar, and amacrine cells within the zebrafish retina. J. Comp. Neurol. 477, 371–385 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Li, Y. N., Tsujimura, T., Kawamura, S. & Dowling, J. E. Bipolar cell-photoreceptor connectivity in the zebrafish (Danio rerio) retina. J. Comp. Neurol. 520, 3786–3802 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cajal, S. R.Y. La rétine des vertébrés. La Cellule 9, 119–257 (in French) (1893).

    Google Scholar 

  17. Euler, T., Schneider, H. & Wässle, H. Glutamate responses of bipolar cells in a slice preparation of the rat retina. J. Neurosci. 16, 2934–2944 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Euler, T. & Masland, R. H. Light-evoked responses of bipolar cells in a mammalian retina. J. Neurophysiol. 83, 1817–1829 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Odermatt, B., Nikolaev, A. & Lagnado, L. Encoding of luminance and contrast by linear and nonlinear synapses in the retina. Neuron 73, 758–773 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mataruga, A., Kremmer, E. & Muller, F. Type 3a and type 3b OFF cone bipolar cells provide for the alternative rod pathway in the mouse retina. J. Comp. Neurol. 502, 1123–1137 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Puller, C., Ivanova, E., Euler, T., Haverkamp, S. & Schubert, T. OFF bipolar cells express distinct types of dendritic glutamate receptors in the mouse retina. Neuroscience 243, 136–148 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Breuninger, T., Puller, C., Haverkamp, S. & Euler, T. Chromatic bipolar cell pathways in the mouse retina. J. Neurosci. 31, 6504–6517 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ghosh, K. K., Bujan, S., Haverkamp, S., Feigenspan, A. & Wassle, H. Types of bipolar cells in the mouse retina. J. Comp. Neurol. 469, 70–82 (2004).

    Article  PubMed  Google Scholar 

  24. Joo, H. R., Peterson, B. B., Haun, T. J. & Dacey, D. M. Characterization of a novel large-field cone bipolar cell type in the primate retina: evidence for selective cone connections. Vis. Neurosci. 28, 29–37 (2011).

    Article  PubMed  Google Scholar 

  25. Light, A. C. et al. Organizational motifs for ground squirrel cone bipolar cells. J. Comp. Neurol. 520, 2864–2887 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  26. MacNeil, M. A., Heussy, J. K., Dacheux, R. F., Raviola, E. & Masland, R. H. The population of bipolar cells in the rabbit retina. J. Comp. Neurol. 472, 73–86 (2004).

    Article  PubMed  Google Scholar 

  27. Baden, T. et al. A tale of two retinal domains: near-optimal sampling of achromatic contrasts in natural scenes through asymmetric photoreceptor distribution. Neuron 80, 1206–1217 (2013).

    Article  CAS  PubMed  Google Scholar 

  28. Zhang, Y., Kim, I. J., Sanes, J. R. & Meister, M. The most numerous ganglion cell type of the mouse retina is a selective feature detector. Proc. Natl Acad. Sci. USA 109, E2391–E2398 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Bleckert, A., Schwartz, G. W., Turner, M. H., Rieke, F. & Wong, R. O. Visual space is represented by nonmatching topographies of distinct mouse retinal ganglion cell types. Curr. Biol. 24, 310–315 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Haverkamp, S., Haeseleer, F. & Hendrickson, A. A comparison of immunocytochemical markers to identify bipolar cell types in human and monkey retina. Vis. Neurosci. 20, 589–600 (2003).

    Article  PubMed  Google Scholar 

  31. Puller, C., Ondreka, K. & Haverkamp, S. Bipolar cells of the ground squirrel retina. J. Comp. Neurol. 519, 759–774 (2011).

    Article  PubMed  Google Scholar 

  32. Li, W. & DeVries, S. H. Bipolar cell pathways for color and luminance vision in a dichromatic mammalian retina. Nature Neurosci. 9, 669–675 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Schubert, T. et al. Development of presynaptic inhibition onto retinal bipolar cell axon terminals is subclass-specific. J. Neurophysiol. 100, 304–316 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wassle, H., Grunert, U., Martin, P. R. & Boycott, B. B. Immunocytochemical characterization and spatial distribution of midget bipolar cells in the macaque monkey retina. Vision Res. 34, 561–579 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Cuenca, N. et al. The neurons of the ground squirrel retina as revealed by immunostains for calcium binding proteins and neurotransmitters. J. Neurocytol. 31, 649–666 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Puthussery, T., Gayet-Primo, J., Taylor, W. R. & Haverkamp, S. Immunohistochemical identification and synaptic inputs to the diffuse bipolar cell type DB1 in macaque retina. J. Comp. Neurol. 519, 3640–3656 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Connaughton, V. P. Bipolar cells in the zebrafish retina. Vis. Neurosci. 28, 77–93 (2011).

    Article  CAS  PubMed  Google Scholar 

  38. Pang, J. J., Gao, F. & Wu, S. M. Stratum-by-stratum projection of light response attributes by retinal bipolar cells of Ambystoma. J. Physiol. 558, 249–262 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Haverkamp, S., Mockel, W. & Ammermüller, J. Different types of synapses with different spectral types of cones underlie color opponency in a bipolar cell of the turtle retina. Vis. Neurosci. 16, 801–809 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Masland, R. H. The neuronal organization of the retina. Neuron 76, 266–280 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ozuysal, Y. & Baccus, S. A. Linking the computational structure of variance adaptation to biophysical mechanisms. Neuron 73, 1002–1015 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nikolaev, A., Leung, K. M., Odermatt, B. & Lagnado, L. Synaptic mechanisms of adaptation and sensitization in the retina. Nature Neurosci. 16, 934–941 (2013).

    Article  CAS  PubMed  Google Scholar 

  43. Manookin, M. B. & Demb, J. B. Presynaptic mechanism for slow contrast adaptation in mammalian retinal ganglion cells. Neuron 50, 453–464 (2006).

    Article  CAS  PubMed  Google Scholar 

  44. Baden, T., Euler, T., Weckstrom, M. & Lagnado, L. Spikes and ribbon synapses in early vision. Trends Neurosci. 36, 480–488 (2013).

    Article  CAS  PubMed  Google Scholar 

  45. Taylor, W. R. & Smith, R. G. Trigger features and excitation in the retina. Curr. Opin. Neurobiol. 21, 672–678 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hack, I., Peichl, L. & Brandstätter, J. H. An alternative pathway for rod signals in the rodent retina: rod photoreceptors, cone bipolar cells, and the localization of glutamate receptors. Proc. Natl Acad. Sci. USA 96, 14130–14135 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fyk-Kolodziej, B., Qin, P. & Pourcho, R. G. Identification of a cone bipolar cell in cat retina which has input from both rod and cone photoreceptors. J. Comp. Neurol. 464, 104–113 (2003).

    Article  PubMed  Google Scholar 

  48. Haverkamp, S. et al. Type 4 OFF cone bipolar cells of the mouse retina express calsenilin and contact cones as well as rods. J. Comp. Neurol. 507, 1087–1101 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Li, W., Chen, S. & DeVries, S. H. A fast rod photoreceptor signaling pathway in the mammalian retina. Nature Neurosci. 13, 414–416 (2010).

    Article  CAS  PubMed  Google Scholar 

  50. Koike, C., Numata, T., Ueda, H., Mori, Y. & Furukawa, T. TRPM1: a vertebrate TRP channel responsible for retinal ON bipolar function. Cell Calcium 48, 95–101 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Regus-Leidig, H. & Brandstatter, J. H. Structure and function of a complex sensory synapse. Acta Physiol. 204, 479–486 (2012).

    Article  CAS  Google Scholar 

  52. DeVries, S. H. Bipolar cells use kainate and AMPA receptors to filter visual information into separate channels. Neuron 28, 847–856 (2000).

    Article  CAS  PubMed  Google Scholar 

  53. Lindstrom, S. H., Ryan, D. G., Shi, J. & Devries, S. H. Kainate receptor subunit diversity underlying response diversity in retinal Off bipolar cells. J. Physiol. 592, 1457–1477 (2014). A detailed dissection of how OFF bipolar cell types (in the ground squirrel) inherit different kinetic properties based on differential expression of glutamate receptor types on their dendrites.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Borghuis, B. G., Looger, L. L., Tomita, S. & Demb, J. B. Kainate receptors mediate signaling in both transient and sustained off bipolar cell pathways in mouse retina. J. Neurosci. 34, 6128–6139 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Masu, M. et al. Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80, 757–765 (1995).

    Article  CAS  PubMed  Google Scholar 

  56. Cao, Y. et al. Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons. Proc. Natl Acad. Sci. USA 109, 7905–7910 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pearring, J. N. et al. A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP melastatin 1 channel to retinal depolarizing bipolar cell dendrites. J. Neurosci. 31, 10060–10066 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cao, Y. et al. Targeting of RGS7/Gβ5 to the dendritic tips of ON-bipolar cells is independent of its association with membrane anchor R7BP. J. Neurosci. 28, 10443–10449 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Cao, Y. et al. Retina-specific GTPase accelerator RGS11/G β 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons. J. Neurosci. 29, 9301–9313 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jeffrey, B. G. et al. R9AP stabilizes RGS11-G β5 and accelerates the early light response of ON-bipolar cells. Vis. Neurosci. 27, 9–17 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ray, T. A. et al. GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells. J. Neurosci. 34, 6334–6343 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sulaiman, P., Fina, M., Feddersen, R. & Vardi, N. Ret-PCP2 colocalizes with protein kinase C in a subset of primate ON cone bipolar cells. J. Comp. Neurol. 518, 1098–1112 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Xu, Y. et al. Retinal ON bipolar cells express a new PCP2 splice variant that accelerates the light response. J. Neurosci. 28, 8873–8884 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. De Sevilla Müller, L. P., Liu, J., Solomon, A., Rodriguez, A. & Brecha, N. C. Expression of voltage-gated calcium channel α2δ4 subunits in the mouse and rat retina. J. Comp. Neurol. 521, 2486–2501 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Sulaiman, P. et al. Kir2.4 surface expression and basal current are affected by heterotrimeric G-proteins. J. Biol. Chem. 288, 7420–7429 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rampino, M. A. & Nawy, S. A. Relief of Mg2+-dependent inhibition of TRPM1 by PKCα at the rod bipolar cell synapse. J. Neurosci. 31, 13596–13603 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Morgans, C. W. et al. TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proc. Natl Acad. Sci. USA 106, 19174–19178 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Koike, C. et al. TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proc. Natl Acad. Sci. USA 107, 332–337 (2010). References 67 and 68 first showed that TRPM1 is the cation channel that lies downstream of the mGluR6 signalling cascade in mouse ON bipolar cells.

    Article  CAS  PubMed  Google Scholar 

  69. Gilliam, J. C. & Wensel, T. G. TRP channel gene expression in the mouse retina. Vision Res. 51, 2440–2452 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Haverkamp, S., Grünert, U. & Wässle, H. Localization of kainate receptors at the cone pedicles of the primate retina. J. Comp. Neurol. 436, 471–486 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Haverkamp, S., Grünert, U. & Wässle, H. The cone pedicle, a complex synapse in the retina. Neuron 27, 85–95 (2000). This study in the macaque provides a demonstration of the complexity of photoreceptor-to-bipolar cell connections.

    Article  CAS  PubMed  Google Scholar 

  72. DeVries, S. H., Li, W. & Saszik, S. Parallel processing in two transmitter microenvironments at the cone photoreceptor synapse. Neuron 50, 735–748 (2006). A study in ground squirrels that provides evidence for the notion that functional differences in bipolar cell types may in part result from different contact morphologies with cones.

    Article  CAS  PubMed  Google Scholar 

  73. Vardi, N., Duvoisin, R., Wu, G. & Sterling, P. Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. J. Comp. Neurol. 423, 402–412 (2000).

    Article  CAS  PubMed  Google Scholar 

  74. Neitz, J. & Neitz, M. The genetics of normal and defective color vision. Vision Res. 51, 633–651 (2011).

    Article  CAS  PubMed  Google Scholar 

  75. Dacey, D. M., Crook, J. D. & Packer, O. S. Distinct synaptic mechanisms create parallel S-ON & S-OFF color opponent pathways in the primate retina. Vis. Neurosci. 31, 1–13 (2013).

    Google Scholar 

  76. Nathans, J. The evolution and physiology of human color vision: insights from molecular genetic studies of visual pigments. Neuron 24, 299–312 (1999).

    Article  CAS  PubMed  Google Scholar 

  77. Wong, K. Y. & Dowling, J. E. Retinal bipolar cell input mechanisms in giant danio. III. ON-OFF bipolar cells and their color-opponent mechanisms. J. Neurophysiol. 94, 265–272 (2005).

    Article  PubMed  Google Scholar 

  78. Dunn, F. A. & Wong, R. O. Diverse strategies engaged in establishing stereotypic wiring patterns among neurons sharing a common input at the visual system's first synapse. J. Neurosci. 32, 10306–10317 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Lee, S. C. & Grünert, U. Connections of diffuse bipolar cells in primate retina are biased against S-cones. J. Comp. Neurol. 502, 126–140 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Mariani, A. P. Bipolar cells in monkey retina selective for the cones likely to be blue-sensitive. Nature 308, 184–186 (1984).

    Article  CAS  PubMed  Google Scholar 

  81. Puller, C. & Haverkamp, S. Bipolar cell pathways for color vision in non-primate dichromats. Vis. Neurosci. 28, 51–60 (2011).

    Article  PubMed  Google Scholar 

  82. Mills, S. L., Tian, L. M., Hoshi, H., Whitaker, C. M. & Massey, S. C. Three distinct blue-green color pathways in a mammalian retina. J. Neurosci. 34, 1760–1768 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Polyak, S. L. The Retina (University of Chicago Press, 1941).

    Google Scholar 

  84. Kryger, Z., Galli-Resta, L., Jacobs, G. H. & Reese, B. E. The topography of rod and cone photoreceptors in the retina of the ground squirrel. Vis. Neurosci. 15, 685–691 (1998).

    Article  CAS  PubMed  Google Scholar 

  85. Thoreson, W. B. & Mangel, S. C. Lateral interactions in the outer retina. Prog. Retin. Eye Res. 31, 407–441 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Vardi, N., Zhang, L. L., Payne, J. A. & Sterling, P. Evidence that different cation chloride cotransporters in retinal neurons allow opposite responses to GABA. J. Neurosci. 20, 7657–7663 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Duebel, J. et al. Two-photon imaging reveals somatodendritic chloride gradient in retinal ON-type bipolar cells expressing the biosensor Clomeleon. Neuron 49, 81–94 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Miller, R. F. & Dacheux, R. F. Intracellular chloride in retinal neurons: measurement and meaning. Vision Res. 23, 399–411 (1983).

    Article  CAS  PubMed  Google Scholar 

  89. Gollisch, T. & Meister, M. Eye smarter than scientists believed: neural computations in circuits of the retina. Neuron 65, 150–164 (2010). A key review that discusses how retinal feature extraction relies heavily on non-linearities in bipolar cell processing.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Schwartz, G. W. et al. The spatial structure of a nonlinear receptive field. Nature Neurosci. 15, 1572–1580 (2012). A demonstration of how comparatively simple cascade models may account for a substantial fraction of mouse RGC response variance under complex stimulation.

    Article  CAS  PubMed  Google Scholar 

  91. Baccus, S. A. & Meister, M. Fast and slow contrast adaptation in retinal circuitry. Neuron 36, 909–919 (2002).

    Article  CAS  PubMed  Google Scholar 

  92. Spruston, N., Jaffe, D. B. & Johnston, D. Dendritic attenuation of synaptic potentials and currents: the role of passive membrane properties. Trends Neurosci. 17, 161–166 (1994).

    Article  CAS  PubMed  Google Scholar 

  93. Sherry, D. M. & Yazulla, S. Goldfish bipolar cells and axon terminal patterns: a Golgi study. J. Comp. Neurol. 329, 188–200 (1993).

    Article  CAS  PubMed  Google Scholar 

  94. Baden, T. & Euler, T. Early vision: where (some of) the magic happens. Curr. Biol. 23, R1096–R1098 (2013).

    Article  CAS  PubMed  Google Scholar 

  95. Burrone, J. & Lagnado, L. Electrical resonance and Ca2+ influx in the synaptic terminal of depolarizing bipolar cells from the goldfish retina. J. Physiol. 505, 571–584 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Protti, D. A., Flores-Herr, N. & von Gersdorff, H. Light evokes Ca2+ spikes in the axon terminal of a retinal bipolar cell. Neuron 25, 215–227 (2000). The first study to demonstrate that light can drive spikes in retinal bipolar cells (the study was conducted in goldfish).

    Article  CAS  PubMed  Google Scholar 

  97. Baden, T., Esposti, F., Nikolaev, A. & Lagnado, L. Spikes in retinal bipolar cells phase-lock to visual stimuli with millisecond precision. Curr. Biol. 21, 1859–1869 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Cui, J. & Pan, Z. H. Two types of cone bipolar cells express voltage-gated Na+ channels in the rat retina. Vis. Neurosci. 25, 635–645 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  99. Saszik, S. & DeVries, S. H. A mammalian retinal bipolar cell uses both graded changes in membrane voltage and all-or-nothing Na+ spikes to encode light. J. Neurosci. 32, 297–307 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Hu, H. J. & Pan, Z. H. Differential expression of K+ currents in mammalian retinal bipolar cells. Vis. Neurosci. 19, 163–173 (2002).

    Article  PubMed  Google Scholar 

  101. Okada, T., Horiguchi, H. & Tachibana, M. Ca2+-dependent Cl current at the presynaptic terminals of goldfish retinal bipolar cells. Neurosci. Res. 23, 297–303 (1995).

    Article  CAS  PubMed  Google Scholar 

  102. Connaughton, V. P. & Maguire, G. Differential expression of voltage-gated K+ and Ca2+ currents in bipolar cells in the zebrafish retinal slice. Eur. J. Neurosci. 10, 1350–1362 (1998).

    Article  CAS  PubMed  Google Scholar 

  103. Müller, F. et al. HCN channels are expressed differentially in retinal bipolar cells and concentrated at synaptic terminals. Eur. J. Neurosci. 17, 2084–2096 (2003).

    Article  PubMed  Google Scholar 

  104. Euler, T. & Wässle, H. Different contributions of GABAA and GABAC receptors to rod and cone bipolar cells in a rat retinal slice preparation. J. Neurophysiol. 79, 1384–1395 (1998).

    Article  CAS  PubMed  Google Scholar 

  105. Eggers, E. D., McCall, M. A. & Lukasiewicz, P. D. Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina. J. Physiol. 582, 569–582 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ivanova, E., Müller, U. & Wässle, H. Characterization of the glycinergic input to bipolar cells of the mouse retina. Eur. J. Neurosci. 23, 350–364 (2006).

    Article  PubMed  Google Scholar 

  107. Vigh, J., Vickers, E. & von Gersdorff, H. Light-evoked lateral GABAergic inhibition at single bipolar cell synaptic terminals is driven by distinct retinal microcircuits. J. Neurosci. 31, 15884–15893 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Masland, R. H. The tasks of amacrine cells. Vis. Neurosci. 29, 3–9 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Esposti, F., Johnston, J., Rosa, J. M., Leung, K. M. & Lagnado, L. Olfactory stimulation selectively modulates the OFF pathway in the retina of zebrafish. Neuron 79, 97–110 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Yang, J., Pahng, J. & Wang, G. Y. Dopamine modulates the off pathway in light-adapted mouse retina. J. Neurosci. Res. 91, 138–150 (2013).

    CAS  PubMed  Google Scholar 

  111. Tooker, R. E. et al. Nitric oxide mediates activity-dependent plasticity of retinal bipolar cell output via S-nitrosylation. J. Neurosci. 33, 19176–19193 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Ayoub, G. S. & Matthews, G. Substance P modulates calcium current in retinal bipolar neurons. Vis. Neurosci. 8, 539–544 (1992).

    Article  CAS  PubMed  Google Scholar 

  113. Casini, G. et al. Expression of the neurokinin 1 receptor in the rabbit retina. Neuroscience 115, 1309–1321 (2002).

    Article  CAS  PubMed  Google Scholar 

  114. Zenisek, D., Davila, V., Wan, L. & Almers, W. Imaging calcium entry sites and ribbon structures in two presynaptic cells. J. Neurosci. 23, 2538–2548 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Llobet, A., Cooke, A. & Lagnado, L. Exocytosis at the ribbon synapse of retinal bipolar cells studied in patches of presynaptic membrane. J. Neurosci. 23, 2706–2714 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Singer, J. H., Lassova, L., Vardi, N. & Diamond, J. S. Coordinated multivesicular release at a mammalian ribbon synapse. Nature Neurosci. 7, 826–833 (2004).

    Article  CAS  PubMed  Google Scholar 

  117. Midorikawa, M., Tsukamoto, Y., Berglund, K., Ishii, M. & Tachibana, M. Different roles of ribbon-associated and ribbon-free active zones in retinal bipolar cells. Nature Neurosci. 10, 1268–1276 (2007).

    Article  CAS  PubMed  Google Scholar 

  118. tom Dieck, S. & Brandstätter, J. H. Ribbon synapses of the retina. Cell Tissue Res. 326, 339–346 (2006).

    Article  PubMed  Google Scholar 

  119. LoGiudice, L. & Matthews, G. The role of ribbons at sensory synapses. Neuroscientist 15, 380–391 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Beaumont, V., Llobet, A. & Lagnado, L. Expansion of calcium microdomains regulates fast exocytosis at a ribbon synapse. Proc. Natl Acad. Sci. USA 102, 10700–10705 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Jackman, S. L. et al. Role of the synaptic ribbon in transmitting the cone light response. Nature Neurosci. 12, 303–310 (2009). Seminal work on how calcium drives release at a ribbon synapse (in lizards).

    Article  CAS  PubMed  Google Scholar 

  122. Sikora, M. A., Gottesman, J. & Miller, R. F. A computational model of the ribbon synapse. J. Neurosci. Methods 145, 47–61 (2005).

    Article  PubMed  Google Scholar 

  123. Palmer, M. J. Modulation of Ca2+-activated K+ currents and Ca2+-dependent action potentials by exocytosis in goldfish bipolar cell terminals. J. Physiol. 572, 747–762 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Awatramani, G. B. & Slaughter, M. M. Intensity-dependent, rapid activation of presynaptic metabotropic glutamate receptors at a central synapse. J. Neurosci. 21, 741–749 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Veruki, M. L., Morkve, S. H. & Hartveit, E. Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling. Nature Neurosci. 9, 1388–1396 (2006).

    Article  CAS  PubMed  Google Scholar 

  126. Guerrero, G. et al. Heterogeneity in synaptic transmission along a Drosophila larval motor axon. Nature Neurosci. 8, 1188–1196 (2005).

    Article  CAS  PubMed  Google Scholar 

  127. Euler, T. & Denk, W. Dendritic processing. Curr. Opin. Neurobiol. 11, 415–422 (2001).

    Article  CAS  PubMed  Google Scholar 

  128. Baden, T. & Hedwig, B. Primary afferent depolarization and frequency processing in auditory afferents. J. Neurosci. 30, 14862–14869 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Gaudry, Q., Hong, E. J., Kain, J., de Bivort, B. L. & Wilson, R. I. Asymmetric neurotransmitter release enables rapid odour lateralization in Drosophila. Nature 493, 424–428 (2013).

    Article  CAS  PubMed  Google Scholar 

  130. Asari, H. & Meister, M. Divergence of visual channels in the inner retina. Nature Neurosci. 15, 1581–1589 (2012). A study in salamanders that provides the first evidence that individual bipolar cells may have different synaptic transfer functions according to the different postsynaptic partners.

    Article  CAS  PubMed  Google Scholar 

  131. Asari, H. & Meister, M. The projective field of retinal bipolar cells and its modulation by visual context. Neuron 81, 641–652 (2014). This study presents evidence that individual salamander bipolar cells functionally feed into an unexpectedly large number and variety of postsynaptic circuits.

    Article  CAS  PubMed  Google Scholar 

  132. Sumbul, U. et al. A genetic and computational approach to structurally classify neuronal types. Nature Commun. 5, 3512 (2014).

    Article  CAS  Google Scholar 

  133. Sun, W., Li, N. & He, S. Large-scale morphological survey of mouse retinal ganglion cells. J. Comp. Neurol. 451, 115–126 (2002).

    Article  PubMed  Google Scholar 

  134. Volgyi, B., Chheda, S. & Bloomfield, S. A. Tracer coupling patterns of the ganglion cell subtypes in the mouse retina. J. Comp. Neurol. 512, 664–687 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  135. Roska, B. & Werblin, F. Vertical interactions across ten parallel, stacked representations in the mammalian retina. Nature 410, 583–587 (2001). Key work in rabbits on the functional stratification rules of the IPL.

    Article  CAS  PubMed  Google Scholar 

  136. Awatramani, G. B. & Slaughter, M. M. Origin of transient and sustained responses in ganglion cells of the retina. J. Neurosci. 20, 7087–7095 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Field, G. D. et al. Functional connectivity in the retina at the resolution of photoreceptors. Nature 467, 673–677 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Chen, S. & Li, W. A color-coding amacrine cell may provide a blue-off signal in a mammalian retina. Nature Neurosci. 15, 954–956 (2012).

    Article  CAS  PubMed  Google Scholar 

  139. Borst, A. & Euler, T. Seeing things in motion: models, circuits, and mechanisms. Neuron 71, 974–994 (2011).

    Article  CAS  PubMed  Google Scholar 

  140. Briggman, K. L., Helmstaedter, M. & Denk, W. Wiring specificity in the direction-selectivity circuit of the retina. Nature 471, 183–188 (2011).

    Article  CAS  PubMed  Google Scholar 

  141. Hausselt, S. E., Euler, T., Detwiler, P. B. & Denk, W. A dendrite-autonomous mechanism for direction selectivity in retinal starburst amacrine cells. PLoS Biol. 5, e185 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Oesch, N., Euler, T. & Taylor, W. R. Direction-selective dendritic action potentials in rabbit retina. Neuron 47, 739–750 (2005).

    Article  CAS  PubMed  Google Scholar 

  143. Schachter, M. J., Oesch, N., Smith, R. G. & Taylor, W. R. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell. PLoS Comput. Biol. 6, e1000899 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Sivyer, B. & Williams, S. R. Direction selectivity is computed by active dendritic integration in retinal ganglion cells. Nature Neurosci. 16, 1848–1856 (2013).

    Article  CAS  PubMed  Google Scholar 

  145. Kim, J. S. et al. Space–time wiring specificity supports direction selectivity in the retina. Nature 509, 331–336 (2014). A demonstration in mice that OFF starburst amacrine cells tend to receive inputs from different types of bipolar cells depending on dendritic eccentricity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Garvert, M. M. & Gollisch, T. Local and global contrast adaptation in retinal ganglion cells. Neuron 77, 915–928 (2013).

    Article  CAS  PubMed  Google Scholar 

  147. Bolinger, D. & Gollisch, T. Closed-loop measurements of iso-response stimuli reveal dynamic nonlinear stimulus integration in the retina. Neuron 73, 333–346 (2012).

    Article  PubMed  CAS  Google Scholar 

  148. Volgyi, B., Deans, M. R., Paul, D. L. & Bloomfield, S. A. Convergence and segregation of the multiple rod pathways in mammalian retina. J. Neurosci. 24, 11182–11192 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Bloomfield, S. A. & Dacheux, R. F. Rod vision: pathways and processing in the mammalian retina. Prog. Retin. Eye Res. 20, 351–384 (2001).

    Article  CAS  PubMed  Google Scholar 

  150. Dunn, F. A. & Rieke, F. The impact of photoreceptor noise on retinal gain controls. Curr. Opin. Neurobiol. 16, 363–370 (2006).

    Article  CAS  PubMed  Google Scholar 

  151. Tsukamoto, Y., Morigiwa, K., Ueda, M. & Sterling, P. Microcircuits for night vision in mouse retina. J. Neurosci. 21, 8616–8623 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Tsukamoto, Y. & Omi, N. Functional allocation of synaptic contacts in microcircuits from rods via rod bipolar to AII amacrine cells in the mouse retina. J. Comp. Neurol. 521, 3541–3555 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Roehlich, P., Van Veen, T. & Szél, A. Two different visual pigments in one retinal cone cell. Neuron 13, 1159–1166 (1994).

    Article  CAS  Google Scholar 

  154. Puller, C., Haverkamp, S. & Grünert, U. OFF midget bipolar cells in the retina of the marmoset, Callithrix jacchus, express AMPA receptors. J. Comp. Neurol. 502, 442–454 (2007).

    Article  CAS  PubMed  Google Scholar 

  155. Haverkamp, S. et al. The primordial, blue-cone color system of the mouse retina. J. Neurosci. 25, 5438–5445 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Neves, G. & Lagnado, L. The kinetics of exocytosis and endocytosis in the synaptic terminal of goldfish retinal bipolar cells. J. Physiol. 515, 181–202 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Pang, J. J., Gao, F. & Wu, S. M. Light-evoked excitatory and inhibitory synaptic inputs to ON and OFF α ganglion cells in the mouse retina. J. Neurosci. 23, 6063–6073 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Kim, I. J., Zhang, Y., Yamagata, M., Meister, M. & Sanes, J. R. Molecular identification of a retinal cell type that responds to upward motion. Nature 452, 478–482 (2008).

    Article  CAS  PubMed  Google Scholar 

  159. van Wyk, M., Taylor, W. R. & Vaney, D. I. Local edge detectors: a substrate for fine spatial vision at low temporal frequencies in rabbit retina. J. Neurosci. 26, 13250–13263 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Ichinose, T., Fyk-Kolodziej, B. & Cohn, J. Roles of on cone bipolar cell subtypes in temporal coding in the mouse retina. J. Neurosci. 34, 8761–8771 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (Werner Reichardt Centre for Integrative Neuroscience Tübingen, EXC 307 to T.E. and T.S.; and HA-5277/2-2 to S.H.), the German Federal Ministry of Education and Research (BMBF) (BCCN Tübingen, FKZ 01GQ1002 to T.E and T.B.), the fortüne programme of the Faculty of Medicine Tübingen (2125-0-0 to T.B.), and the BW-Stiftung (AZ 1.16101.09 to T.B.).

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Supplementary information

Supplementary information S1 (figure)

Organization of the bipolar cell types in the mouse retina. (PDF 550 kb)

Supplementary information S2 (table)

Immunomarkers and transgenic lines for mouse bipolar cells (PDF 202 kb)

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Glossary

Bistratified

This term describes bipolar cells that send projections to two strata within the retina's inner plexiform layer.

Tristratified

This term describes bipolar cells that send projections to three strata within the retina's inner plexiform layer.

Opsins

Light-sensitive G protein-coupled receptors that are expressed in photoreceptors. Different opsin types are sensitive to different wavelengths of light, and thus comparing the responses of spectrally distinct types forms the basis of colour vision. In addition to rhodopsin, the opsin of the rod photoreceptors, mammals express up to three types of cone opsins: short-, mid- and long-wavelength-sensitive opsins.

Isopotential

This term is used here to describe a single neuronal compartment that does not exhibit local voltage differences.

Poisson process

A stochastic process that counts the number of events and their timing. Inter-arrival times between each pair of consecutive events have an exponential distribution and are independent.

Linear–non-linear model

A simplified model of neural responses to an arbitrary stimulus that is based on a sequential set-up of a linear operation followed by a non-linear operation.

Ribbons

Specialized presynaptic structures found in some sensory neurons — including bipolar cells and photoreceptors — that promote the trafficking and fusion of synaptic vesicles at the active zone.

Multiplexing

This term is used to denote the idea that a single neuron may relay different synaptic signals to different postsynaptic partners.

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Euler, T., Haverkamp, S., Schubert, T. et al. Retinal bipolar cells: elementary building blocks of vision. Nat Rev Neurosci 15, 507–519 (2014). https://doi.org/10.1038/nrn3783

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