Non-linearities in the Rod and Cone Photoreceptor Inputs to the Afferent Pupil Light Response

Front Neurol. 2018 Dec 21;9:1140. doi: 10.3389/fneur.2018.01140. eCollection 2018.

Abstract

Purpose: To assess the nature and extent of non-linear processes in pupil responses using rod- and cone-isolating visual beat stimuli. Methods: A four-primary photostimulating method based on the principle of silent substitution was implemented to generate rod or cone isolating and combined sinusoidal stimuli at a single component frequency (1, 4, 5, 8, or 9 Hz) or a 1 Hz beat frequency (frequency pairs: 4 + 5, 8 + 9 Hz). The component frequencies were chosen to minimize the melanopsin photoresponse of intrinsically photosensitive retinal ganglion cells (ipRGCs) such that the pupil response was primarily driven by outer retinal photoreceptor inputs. Full-field (Ganzfeld) pupil responses and electroretinograms (ERGs) were recorded to the same stimuli at two mesopic light levels (-0.9 and 0 log cd/m2). Fourier analysis was used to derive the amplitudes and phases of the pupil and ERG responses. Results: For the beat frequency condition, when modulation was restricted to the same photoreceptor type at the higher mesopic level (0 log cd/m2), there was a pronounced pupil response to the 1 Hz beat frequency with the 4 + 5 Hz frequency pair and rare beat responses for the 8 + 9 Hz frequency pair. At the lower mesopic level there were few and inconsistent beat responses. When one component modulated the rod excitation and the other component modulated the cone excitation, responses to the beat frequency were rare and lower than the 1 Hz component frequency condition responses. These results were confirmed by ERG recordings. Conclusions: There is non-linearity in both the pupil response and electroretinogram to rod and cone inputs at mesopic light levels. The presence of a beat response for modulation components restricted to a single photoreceptor type, but not for components with cross-photoreceptor types, indicates that the location of a non-linear process in the pupil pathway occurs at a retinal site earlier than where the rod and cone signals are combined, that is, at the photoreceptor level.

Keywords: ERG analysis; beats; mesopic light level; non-linearity; photoreceptors cells; pupil; retina.