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A neuronal circuit for colour vision based on rod–cone opponency

Nature volume 532, pages 236–239 (2016)Cite this article

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Abstract

In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have ‘colour-opponent’ visual responses—excited by light of one colour and suppressed by another colour1. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals2. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC)3, was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a ‘blue shift’ in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.

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Figure 1: A spectrally opponent pathway in the mouse retina.
Figure 2: Rod–cone antagonism.
Figure 3: Synaptic pathways for spectral opponency.

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Acknowledgements

We thank E. Soucy and J. Greenwood for technical support, J. Cauceglia for providing the urine post samples, J. R. Sanes and E. Soucy for comments on the manuscript. This work was supported by grants to M.M. from the NIH and to M.J. from The International Human Frontier Science Program Organization.

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Authors and Affiliations

  1. Harvard University, 52 Oxford Street, Cambridge, 02138, Massachusetts, USA

    Maximilian Joesch

  2. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, 91125, California, USA

    Markus Meister

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Contributions

M.J. designed the study, performed all experiments, interpreted results, and wrote the manuscript. M.M. helped design the study, interpret results, and wrote the manuscript.

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Correspondence to Maximilian Joesch or Markus Meister.

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Extended data figures and tables

Extended Data Figure 1 Spiking responses to chromatic centre and surround stimuli.

a, Summary of responses to centre (left) and surround (right), derived from the experiment of Fig. 1d. Peak firing rate to an ON flash was subtracted from that to the OFF flash, and averaged over cells (n = 7; mean ± s.e.m.). Green light acts almost exclusively in the surround, UV light only in the centre. b, Response of a non-opponent J-RGC to a flashed spot or annulus (as in Fig. 1c). c, Summary of the differential response for non-opponent cells (n = 8, ± s.e.m.) displayed as in a. Green light and UV light act with the same polarity, OFF in centre, ON in surround. Note that both lights excite the M cone that is prevalent in the dorsal retina.

Extended Data Figure 2 Spectra of the visual stimuli.

a, Normalized absorption spectra of mouse photoreceptors (black trace: rhodopsin; green: M opsin; blue: S opsin). Overlaid, the normalized emission spectra of the UV and green light emitted by the DLP projector (filled blue: UV, filled green: green light). b, Isomerization rate per photoreceptor in rods (black), M cones (green) and S cones (blue). The collecting area for cones was 0.2 μm2, for rods see Methods.

Extended Data Figure 3 Responses of non-opponent J-RGCs in dorsal retina.

a, Centre surround antagonism for non-opponent J-RGCs, at intermediate (top) and high (bottom) intensity. Each curve shows the peak firing rate in response to flashing spots of increasing size, measured separately at light onset (ON) and offset (OFF). Data were normalized for each cell and averaged over 7–14 cells (mean ± s.e.m.). b, c, Time course and spatial profile of the receptive field at different photopic intensities, averaged over 20 or 32 cells, respectively, and displayed as in Fig. 1e, f. d, Time course of excitatory (left) and inhibitory (right) conductance changes from stimulation of the S (blue trace) and M/rod-pigments (green) in the receptive field centre (top) and surround (bottom) (non-opponent cells n = 5, displayed as in Fig. 3a). e, Opsin space histogram for centre (top) and surround (bottom) currents (black: excitation, grey: inhibition). Note similarity to results from opponent J-RGCs (Fig. 3), except that the centre is driven by M pigment, as expected given the paucity of S cones in the dorsal region. The surround again has a pure M spectrum and produces both presynaptic and post-synaptic inhibition, with dynamics that are virtually identical to the signals in ventral J-RGCs.

Extended Data Figure 4 J-RGC current responses to flashed spots and annuli.

a, Inhibitory and excitatory currents of a spectrally opponent J-RGC to a flashed spot (top, 250 μm diameter) and annulus (bottom, 2,000 μm and 350 μm for outer and inner diameter, respectively) centred on the receptive field using UV, green, or white (green + UV) light. b, c, Peak currents measured to a white flashed spot and annulus (b, inhibition, ON spot & OFF annulus; c, excitation, OFF spot & ON annulus; stimulus dimensions as in a) in control (black), picrotoxin (PTX, 100 μM; red), and combined (brown) PTX (100 μM) and strychnine (STR, 10 μM). Circles: individual cells; means ± s.e.m.; n.s.: not significant, *P < 0.05, ***P < 0.001, one-way ANOVA. Note the synaptic currents in J-RGCs are systematically smaller (for example, excitatory current from centre stimulation = 10–20 pA) than those measured in other RGC types (for example, 500–1,000 pA typical in sustained alpha cells) during the same recording session.

Extended Data Figure 5 Synaptic pathways for spectral opponency (single cell examples).

a, d, g, j, m, Inhibitory and excitatory currents during white-noise flicker stimulation of three different J-RGCs before and after drug application (shaded grey depicts the start of white-noise stimulus; a, d, L-AP4 11 μM; g, j, PTX 100 μM; m, L-AP4 11 μM, PTX 100 μM and STR 10 μM). b, e, h, k, n, Single cell excitatory and inhibitory current distribution under white-noise stimulation (before and during drug application). Inhibitory current distribution is dramatically narrowed during L-AP4 and PTX application, the excitatory current distribution remains comparatively unaltered. c, f, i, l, o, Single cell visual sensitivity of synaptic currents recorded from the respective J-RGC recordings in the left panels (as in Fig. 3a). Excitatory and inhibitory conductances are driven by stimulation of the centre (left) or surround (right) of the receptive field. Each curve represents the sensitivity of the conductance to stimulation of the M/rod pigment (green) or S pigment (blue) at various times in the past (see Methods).

Extended Data Figure 6 J-RGCs in a mutant retina with silenced cones.

Responses of J-RGCs in the ventral retina of homozygous Gnat2cpfl3 mutant mice. Flashing spots and annuli as in Fig. 1d. a, Raster graph of spiking for one sample neuron. b, Summary of responses from 5 neurons. Firing rate normalized to that under ‘surround ON’ stimulation. Note little or no response to centre stimulation. Compare to wild-type retina in Figs 1d and 2d and Extended Data Fig. 1.

Extended Data Figure 7 Spectrally opponent features in the environment.

Dried mouse urine and plant seeds have high S-M chromatic contrast. a–c, On a background of clean mouse bedding are two dishes containing bedding soiled with urine (left) and a mix of plant seeds (right). Photographs used a band-pass filter in the ultraviolet (a) and in the green (b); c merges the two using red-green encoding. d, Close-up view of mouse urinating posts (reproduced with permission from ref. 26; 2.5–3.5 cm high). e, Normalized spectra of indirect sunlight and light reflected from a mixture of untreated plant seeds and urine posts. f, Pigment absorption curves for S opsin (blue) and M opsin (green) multiplied by the ocular transmission spectrum (see Methods). Shaded region indicates pass band of the filters used for a–c.

Extended Data Figure 8 UV-green colour signature of urine.

a, Pigment absorption curves for S opsin (blue) and M opsin (green) multiplied by the ocular transmission spectrum (see Methods) and spectra of light reflected from a Whatman filter paper, with or without dried urine marks, under indirect sunlight. b, Normalized curves of the product between the above absorption and reflectance spectra. Blue: S opsin, green: M opsin, solid line: clean filter paper, filled area: filter paper with urine. Note that the reduction in the S-band is 27.4%, compared to only 8.2% for the M-band.

Extended Data Figure 9 Effects of the light flash exposure for fluorescent targeting.

Temporal filter in the receptive field centre and surround for S opsin and M/rod opsin (as in Fig. 1f; blue and green traces, respectively) of three RGCs taken before and after one or two brief light flashes. These neurons were targeted blindly and are therefore not of the J-RGC type. They rely on both rods and cones (note different spectral sensitivity in the centre and surround). Yet their response properties were not altered by the brief flashes.

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Joesch, M., Meister, M. A neuronal circuit for colour vision based on rod–cone opponency. Nature 532, 236–239 (2016). https://doi.org/10.1038/nature17158

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