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Retinal output changes qualitatively with every change in ambient illuminance

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Abstract

The collective activity pattern of retinal ganglion cells, the retinal code, underlies higher visual processing. How does the ambient illuminance of the visual scene influence this retinal output? We recorded from isolated mouse and pig retina and from mouse dorsal lateral geniculate nucleus in vivo at up to seven ambient light levels covering the scotopic to photopic regimes. Across each luminance transition, most ganglion cells exhibited qualitative response changes, whereas they maintained stable responses within each luminance. We commonly observed the appearance and disappearance of ON responses in OFF cells and vice versa. Such qualitative response changes occurred for a variety of stimuli, including full-field and localized contrast steps and naturalistic movies. Our results suggest that the retinal code is not fixed but varies with every change of ambient luminance. This finding raises questions about signal processing within the retina and has implications for visual processing in higher brain areas.

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Figure 1: Overview of experimental procedure.
Figure 2: Early and delayed anti-preferred responses.
Figure 3: Summary of luminance-dependent response types.
Figure 4: Responses (firing rate) of two ON ganglion cells.
Figure 5: Stability of responses at individual light levels.
Figure 6: Responses recorded from individual ganglion cells.
Figure 7: Luminance-dependent qualitative response changes in the dLGN.
Figure 8: Luminance-dependent response changes to small localized disk stimuli.

References

  1. 1

    O'Brien, B.J., Isayama, T., Richardson, R. & Berson, D.M. Intrinsic physiological properties of cat retinal ganglion cells. J. Physiol. (Lond.) 538, 787–802 (2002).

    Article  CAS  Google Scholar 

  2. 2

    Gollisch, T. & Meister, M. Eye smarter than scientists believed: neural computations in circuits of the retina. Neuron 65, 150–164 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Reitner, A., Sharpe, L.T. & Zrenner, E. Is colour vision possible with only rods and blue-sensitive cones? Nature 352, 798–800 (1991).

    Article  CAS  Google Scholar 

  4. 4

    Enroth-Cugell, C. & Lennie, P. The control of retinal ganglion cell discharge by receptive field surrounds. J. Physiol. (Lond.) 247, 551–578 (1975).

    Article  CAS  Google Scholar 

  5. 5

    Farrow, K. et al. Ambient illumination toggles a neuronal circuit switch in the retina and visual perception at cone threshold. Neuron 78, 325–338 (2013).

    Article  CAS  Google Scholar 

  6. 6

    Sagdullaev, B.T. & McCall, M.A. Stimulus size and intensity alter fundamental receptive-field properties of mouse retinal ganglion cells in vivo. Vis. Neurosci. 22, 649–659 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7

    Grimes, W.N., Schwartz, G.W. & Rieke, F. The synaptic and circuit mechanisms underlying a change in spatial encoding in the retina. Neuron 82, 460–473 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    Umino, Y., Solessio, E. & Barlow, R.B. Speed, spatial, and temporal tuning of rod and cone vision in mouse. J. Neurosci. 28, 189–198 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Protti, D.A., Flores-Herr, N., Li, W., Massey, S.C. & Wassle, H. Light signaling in scotopic conditions in the rabbit, mouse and rat retina: a physiological and anatomical study. J. Neurophysiol. 93, 3479–3488 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10

    Eggers, E.D., Mazade, R.E. & Klein, J.S. Inhibition to retinal rod bipolar cells is regulated by light levels. J. Neurophysiol. 110, 153–161 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    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  PubMed Central  Google Scholar 

  12. 12

    Ke, J.B. et al. Adaptation to background light enables contrast coding at rod bipolar cell synapses. Neuron 81, 388–401 (2014).

    Article  CAS  Google Scholar 

  13. 13

    Dunn, F.A., Doan, T., Sampath, A.P. & Rieke, F. Controlling the gain of rod-mediated signals in the mammalian retina. J. Neurosci. 26, 3959–3970 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Dunn, F.A., Lankheet, M.J. & Rieke, F. Light adaptation in cone vision involves switching between receptor and post-receptor sites. Nature 449, 603–606 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Allen, A.E. et al. Melanopsin-driven light adaptation in mouse vision. Curr. Biol. published online, doi:10.1016/j.cub.2014.09.015 (7 October 2014).

  16. 16

    Manookin, M.B., Beaudoin, D.L., Ernst, Z.R., Flagel, L.J. & Demb, J.B. Disinhibition combines with excitation to extend the operating range of the OFF visual pathway in daylight. J. Neurosci. 28, 4136–4150 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Münch, T.A. et al. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nat. Neurosci. 12, 1308–1316 (2009).

    Article  CAS  Google Scholar 

  18. 18

    Pitkow, X. & Meister, M. Decorrelation and efficient coding by retinal ganglion cells. Nat. Neurosci. 15, 628–635 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Kuffler, S.W. Discharge patterns and functional organization of mammalian retina. J. Neurophysiol. 16, 37–68 (1953).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Farajian, R., Pan, F., Akopian, A., Volgyi, B. & Bloomfield, S.A. Masked excitatory crosstalk between the ON and OFF visual pathways in the mammalian retina. J. Physiol. (Lond.) 589, 4473–4489 (2011).

    Article  CAS  Google Scholar 

  21. 21

    Roska, B. & Werblin, F. Vertical interactions across ten parallel, stacked representations in the mammalian retina. Nature 410, 583–587 (2001).

    Article  CAS  Google Scholar 

  22. 22

    Meister, M. & Berry, M.J. II. The neural code of the retina. Neuron 22, 435–450 (1999).

    Article  CAS  Google Scholar 

  23. 23

    Lamb, T.D. & Pugh, E.N. Jr. Phototransduction, dark adaptation, and rhodopsin regeneration: the Proctor lecture. Invest. Ophthalmol. Vis. Sci. 47, 5137–5152 (2006).

    Article  Google Scholar 

  24. 24

    Werblin, F.S. & Dowling, J.E. Organization of the retina of the mudpuppy, Necturus maculosus. II. Intracellular recording. J. Neurophysiol. 32, 339–355 (1969).

    Article  CAS  Google Scholar 

  25. 25

    Asari, H. & Meister, M. The projective field of retinal bipolar cells and its modulation by visual context. Neuron 81, 641–652 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Lukasiewicz, P.D. Synaptic mechanisms that shape visual signaling at the inner retina. Prog. Brain Res. 147, 205–218 (2005).

    Article  CAS  Google Scholar 

  27. 27

    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 

  28. 28

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

    Article  CAS  Google Scholar 

  29. 29

    Smirnakis, S.M., Berry, M.J., Warland, D.K., Bialek, W. & Meister, M. Adaptation of retinal processing to image contrast and spatial scale. Nature 386, 69–73 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Tkačik, G., Ghosh, A., Schneidman, E. & Segev, R. Adaptation to changes in higher-order stimulus statistics in the salamander retina. PLoS ONE 9, e85841 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Helmstaedter, M. et al. Connectomic reconstruction of the inner plexiform layer in the mouse retina. Nature 500, 168–174 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Lauritzen, J.S. et al. ON cone bipolar cell axonal synapses in the OFF inner plexiform layer of the rabbit retina. J. Comp. Neurol. 521, 977–1000 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

    Geffen, M.N., de Vries, S.E. & Meister, M. Retinal ganglion cells can rapidly change polarity from Off to On. PLoS Biol. 5, e65 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34

    Farrow, K. & Masland, R.H. Physiological clustering of visual channels in the mouse retina. J. Neurophysiol. 105, 1516–1530 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35

    Rockhill, R.L., Daly, F.J., MacNeil, M.A., Brown, S.P. & Masland, R.H. The diversity of ganglion cells in a mammalian retina. J. Neurosci. 22, 3831–3843 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Zeck, G.M. & Masland, R.H. Spike train signatures of retinal ganglion cell types. Eur. J. Neurosci. 26, 367–380 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37

    Dorn, J.D. et al. The detection of motion by blind subjects with the Epiretinal 60-Electrode (Argus II) retinal prosthesis. JAMA Ophthalmol. 131, 183–189 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38

    Wang, L. et al. Photovoltaic retinal prosthesis: implant fabrication and performance. J. Neural Eng. 9, 046014 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39

    Zrenner, E. et al. Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc. Biol. Sci. 278, 1489–1497 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Bi, A. et al. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50, 23–33 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Busskamp, V., Picaud, S., Sahel, J.A. & Roska, B. Optogenetic therapy for retinitis pigmentosa. Gene Ther. 19, 169–175 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Lagali, P.S. et al. Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat. Neurosci. 11, 667–675 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Nirenberg, S. & Pandarinath, C. Retinal prosthetic strategy with the capacity to restore normal vision. Proc. Natl. Acad. Sci. USA 109, 15012–15017 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44

    Cai, C., Twyford, P. & Fried, S. The response of retinal neurons to high-frequency stimulation. J. Neural Eng. 10, 036009 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45

    Jacobs, A.L. et al. Ruling out and ruling in neural codes. Proc. Natl. Acad. Sci. USA 106, 5936–5941 (2009).

    Article  Google Scholar 

  46. 46

    Rathbun, D.L., Alitto, H.J., Weyand, T.G. & Usrey, W.M. Interspike interval analysis of retinal ganglion cell receptive fields. J. Neurophysiol. 98, 911–919 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47

    Berry, M.J., Warland, D.K. & Meister, M. The structure and precision of retinal spike trains. Proc. Natl. Acad. Sci. USA 94, 5411–5416 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Funke, K. & Worgotter, F. On the significance of temporally structured activity in the dorsal lateral geniculate nucleus (LGN). Prog. Neurobiol. 53, 67–119 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Schnitzer, M.J. & Meister, M. Multineuronal firing patterns in the signal from eye to brain. Neuron 37, 499–511 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Paxinos, G. & Franklin, K. The Mouse Brain in Stereotaxic Coordinates (Academic Press, 2001).

  51. 51

    Reinhard, K. et al. Step-by-step instructions for retina recordings with perforated multi electrode arrays. PLoS ONE 9, e106148 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52

    Yonehara, K. et al. Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit. Nature 469, 407–410 (2011).

    Article  CAS  Google Scholar 

  53. 53

    Gavrikov, K.E., Nilson, J.E., Dmitriev, A.V., Zucker, C.L. & Mangel, S.C. Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina. Proc. Natl. Acad. Sci. USA 103, 18793–18798 (2006).

    Article  CAS  Google Scholar 

  54. 54

    Hoover, J.L., Bond, C.E., Hoover, D.B. & Defoe, D.M. Effect of neurturin deficiency on cholinergic and catecholaminergic innervation of the murine eye. Exp. Eye Res. 122, 32–39 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Nikonov, S.S., Kholodenko, R., Lem, J. & Pugh, E.N. Jr. Physiological features of the S- and M-cone photoreceptors of wild-type mice from single-cell recordings. J. Gen. Physiol. 127, 359–374 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56

    Szikra, T. et al. Rods in daylight act as relay cells for cone-driven horizontal cell–mediated surround inhibition. Nat. Neurosci. 10.1038/nn.3852 (26 October 2014).

  57. 57

    Chichilnisky, E.J. A simple white noise analysis of neuronal light responses. Network 12, 199–213 (2001).

    Article  CAS  Google Scholar 

  58. 58

    Lyubarsky, A.L., Daniele, L.L. & Pugh, E.N. Jr. From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG. Vision Res. 44, 3235–3251 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Jacobs, G.H. & Williams, G.A. Contributions of the mouse UV photopigment to the ERG and to vision. Doc. Ophthalmol. 115, 137–144 (2007).

    Article  Google Scholar 

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Acknowledgements

We thank J. Wynne for technical assistance and M. Biel (LMU München) for supplying Cnga3−/− mice. This research was supported by funds of the Deutsche Forschungsgemeinschaft (DFG) to the Werner Reichardt Centre for Integrative Neuroscience (DFG EXC 307), by the Bundesministerium für Bildung and Forschung (BMBF) to the Bernstein Center for Computational Neuroscience (FKZ 01GQ1002), by funds of the Biotechnology and Biological Sciences Research Council (BBSRC BB/1007296/1) and the European Commission (ERC Advanced Grant MeloVision) to R.J.L., a Christiane-Nüsslein-Volhard Stipend to A.T.-H., and a Pro-Retina Stipend to K.R.

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A.T.-H., K.R. and T.A.M. designed the study. MEA recordings and spike sorting were performed by A.T.-H., K.R., H.S. and A.H., and analyzed by A.T.-H., K.R. and T.A.M. Patch-clamp experiments and immunohistochemistry were conducted and analyzed by H.S. and T.A.M. In vivo experiments were designed by C.A.P., A.E.A. and R.J.L., performed by C.A.P. and A.E.A., and analyzed by C.A.P., A.E.A. and K.R. Pig eyes were provided by M.S. The manuscript was prepared by A.T.-H., K.R. and T.A.M. with the help of H.S., C.A.P., A.E.A. and R.J.L.

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Correspondence to Thomas A Münch.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Experimental setup for multi-electrode array recordings.

The retina was placed on a multi-electrode array and visual stimulation was achieved with a projector through the condenser of the microscope. Neutral density (ND) filters were used to decrease the mean luminance of the visual stimulation in 1-log-unit steps.

Supplementary Figure 2 Luminance-dependent response changes with and without GABA blockers.

(a) Stimulus protocol. SR: SR-95531 (gabazine), Pic.: picrotoxin. (be) Examples of luminance- and GABA-blocker-dependent response patterns in three OFF cells (b,d,f) and two ON cell (c,e). Left: Spike rates at ND7 and ND6 luminance levels with and without GABA blockers. Right: One possible circuit scheme each which is consistent with the observed responses. The five examples represent the following categories of observations: (b) Luminance-dependent response changes not influenced by GABA (observed in n = 3 units; the example shows appearing early ON response at ND6 under both control and drug condition). Such cells changed their response properties identically under control and drug conditions between ND7 and ND6. Thus, these luminance-dependent response changes were independent of GABAergic regulation. (c) Luminance-dependent GABAergic masking of responses (n = 3; example cell has a delayed ON response masked at ND7). In such cells, light responses differed at ND7 and ND6 under control conditions, but not in the presence of GABA blockers. This suggests that GABAergic inhibition masked a response at one light level. (d) Luminance-independent GABAergic masking of responses (n = 12; example: unmasked early response at ND7 and ND6). Such cells did not show any luminance-dependent changes, neither in control nor with GABA blockers, but their responses were different between control and drug conditions within each light level. This suggests that GABAergic inhibition regulated responses at both luminance levels. Potentially, these masked responses might be revealed at other brightness levels. Note that the same phenomenon applies to the early ON responses in f. (e) GABA-dependent stabilization of responses (n = 13; the example illustrates this effect for early OFF responses). Such cells with stable responses under control conditions had changing responses under drug conditions. Thus, those changing response themselves were GABA-independent, while at the same time GABA stabilized the responses during the luminance-switch under control conditions. Note that the same phenomenon applies to the delayed ON responses in f. (f) GABA-dependent disinhibition (n = 6, the example shows disappearance of delayed ON response with GABA blockers at ND6). While in all examples above GABA blockers revealed additional responses, in few cells responses disappeared in GABA blockers (n = 2 at ND7, n = 5 at ND6, of which 1 unit was affected at both NDs). This suggests luminance-dependent disinhibitory GABAergic mechanisms.The phenomena described by these examples occurred in both ON and OFF cells. In some cells, we observed one phenomenon to the white step, and another phenomenon to the black step, highlighting the response asymmetry already observed in control conditions (Fig. 3). In summary, we found that the mechanism of GABAergic response regulation is highly diverse, and that it underlies some but not all luminance-dependent qualitative response changes.

Supplementary Figure 3 Luminance-dependent changes in ganglion cell responses to a naturalistic movie.

Raster plots: responses of individual ganglion cells to the movie stimulus (left) and to the full-field step stimulus (right). Shaded regions indicate events where the neuron was silent, even though it responded at other light levels. (a) ON ganglion cell with stable responses to the full-field step, but qualitative changes in its movie response. (b) OFF ganglion cell with changing responses to both movie and full-field step stimulus. (c) Response changes to full-field steps do not always occur together with response changes to movies, and vice versa. Numbers indicate the number of units in each group.

Supplementary Figure 4 Luminance-dependent qualitative response changes in different mouse lines lacking functional cones.

Cpfl1: 98 OFF cells and 148 ON cells from 6 retinas. Cnga3–/–: 62 OFF cells and 93 ON cells from 6 retinas. Gnat2cpfl3: 16 OFF cells and 24 ON cells from 5 retinas. Conventions as in Fig. 3b. Source data

Supplementary Figure 5 Summary of luminance-dependent response types in pig retina.

Data is based on recordings from 27 ON cells and 59 OFF cells from 3 retinal pieces from 2 animals. Conventions as in Fig. 3. Source data

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Tikidji-Hamburyan, A., Reinhard, K., Seitter, H. et al. Retinal output changes qualitatively with every change in ambient illuminance. Nat Neurosci 18, 66–74 (2015). https://doi.org/10.1038/nn.3891

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