The Method of Silent Substitution for Examining Melanopsin Contributions to Pupil Control

Manuel Spitschan, Tom Woelders, Manuel Spitschan, Tom Woelders

Abstract

The human pupillary light response is driven by all classes of photoreceptors in the human eye-the three classes of cones, the rods, and the intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin. These photoreceptor classes have distinct but overlapping spectral tuning, and even a monochromatic light with a wavelength matched to the peak spectral sensitivity of a given photoreceptor will stimulate all photoreceptors. The method of silent substitution uses pairs of lights ("metamers") to selectively stimulate a given class of photoreceptors while keeping the activation of all others constant. In this primer, we describe the method of silent substitution and provide an overview of studies that have used it to examine inputs to the human pupillary light response.

Keywords: color vision; ipRGC (intrinsically photosensitive retinal ganglion cell); melanopsin; metamers; pupil; pupillometry; silent substitution.

Figures

Figure 1
Figure 1
(A) Overlapping spectral sensitivities of the human photoreceptors. (B) Non-specificity of single-wavelength lights. Right panel: Pattern of photoreceptor responses to the single-wavelength light at 490 nm. (C) Principle of univariance. Right panel: Pattern of photoreceptor responses to the single-wavelength lights E1, E2, and E3 designed to elicit the same response in melanopsin. (D) Wavelength exchange between two short-wavelength lights E1 and E2 which stimulate S cones at the same level but yield different photoreceptor responses for melanopsin. Right panel: Pattern of excitations for lights E1 and E2.
Figure 2
Figure 2
(A) Background spectrum (left panel) to which the observer is light-adapted, eliciting a pattern of responses in the photoreceptors (right panel). (B) Increase in emitted light near the melanopsin peak relative to the background spectrum (left panel; dashed line = background spectrum, red line = modulation spectrum) leads to an increase in the excitation of all photoreceptors (middle panel), or equivalently, positive contrast on the photoreceptors (right panel). (C) To balance the excitation of the S cones, a decrease in emitted short-wavelength light (left panel) leads to silencing of the S cones (middle panel), or equivalently, zero contrast on the S cones (right panel). (D) To balance the excitation of the L and M cones, a decrease in emitted medium-wavelength light (left panel) leads to a reduction in L and M cone activity (middle panel) but not yet zero contrast on the L and M cones (right panel); indeed, the contrast seen by the L and M cones is now negative. (E) To silence the excitation of the L and M cones, a decrease in emitted long-wavelength light (left panel) leads to balancing of the L and M cones (middle panel), or equivalently, zero contrast on the L and M cones (right panel). The contrast seen by melanopsin is 50%. (F) The modulation spectrum shown in (E) yields positive contrast relative to the background spectrum but the spectrum can also be “mirrored” around the background spectrum, thereby leading to a negative modulation of melanopsin (and rods).

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