The Contribution of Melanopsin and Cone Photoreceptors to Light-Evoked Activity in the Mouse Olivary Pretectal Nucleus

Abstract

Purpose: : In addition to rod and cone photoreceptors, the retina contains a subset of retinal ganglion cells that are rendered intrinsically photosensitive due to the expression of the photopigment melanopsin. These melanopsin-expressing retinal ganglion cells innervate several central targets, notably those associated with non-image forming light responses. One area is the olivary pretectal nucleus (OPN), a relay-station for the pupillary light reflex. We aimed to characterise the contribution of melanopsin and cone photoreceptors to light-evoked activity within the OPN in vivo.

Methods: : Light-dependent changes in spike-firing rate were assessed via multi-electrode recordings in the pretectum of anaesthetised mice. The contribution of each photoreceptor was initially examined by describing stimulus-response relationships for transgenic mice lacking rods and cones (rd/rd cl) or melanopsin (Opn4^-/-). We further explored the individual contribution of cones using red cone knock-in (Opn1mw^R) mice, which carry a human red cone opsin coding sequence in place of the native medium-wavelength cone opsin. The resultant shift in cone spectral sensitivity allowed us to identify cone-driven responses by their enhanced sensitivity to red light.

Results: : Responses in Opn1mw^R mice to blue light were characterised by strong transient increases in firing rate at lights ON and OFF, and sustained elevations in firing rate for the duration of stimulus presentation. However, sustained responses to red-light stimuli isoluminant for cones were substantially attenuated. In rd/rd cl mice, neurons showed sluggish increases in firing rate that gradually increased to a peak around 10s after stimulus onset, persisting until around 20s after offset. Conversely, Opn4^-/- mice displayed fast ON and OFF transient responses, but relatively little sustained responses during light stimuli.

Conclusions: : These data reveal that while cones (and rods) drive fast transient responses to light onset and offset, melanopsin contributes to sustained elements of light-evoked activity within the OPN, especially at higher light intensities. They further suggest that melanopsin makes a unique contribution to the sensory capabilities of the mammalian visual system.

Keywords: electrophysiology: non-clinical • photoreceptors • pupillary reflex