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Retinal output changes qualitatively with every change in ambient illuminance

Nature Neuroscience volume 18, pages 66–74 (2015)Cite this article

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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.

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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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Author notes

  1. Alexandra Tikidji-Hamburyan

    Present address: Present address: Department of Neurosurgery and Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, USA.,

  2. Alexandra Tikidji-Hamburyan and Katja Reinhard: These authors contributed equally to this work.

Authors and Affiliations

  1. Retinal Circuits and Optogenetics, Centre for Integrative Neuroscience and Bernstein Center for Computational Neuroscience, University of Tübingen, Tübingen, Germany

    Alexandra Tikidji-Hamburyan, Katja Reinhard, Hartwig Seitter, Anahit Hovhannisyan & Thomas A Münch

  2. Faculty of Life Science, University of Manchester, Manchester, UK

    Christopher A Procyk, Annette E Allen & Robert J Lucas

  3. Department for General, Visceral and Transplant Surgery, Institute for Experimental Surgery, University Hospital Tübingen, Tübingen, Germany

    Martin Schenk

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Contributions

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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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. (b–e) 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.

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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.

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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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