Melanopsin-Dependent Non-Visual Responses by Light: Evidence for Photopigment Bistability in vivo

In mammals, non-visual responses to light have been shown to involve intrinsically photosensitive retinal ganglion cells (ipRGC) that express melanopsin and that are modulated by input from both rods and cones. Recent in vitro evidence suggests that melanopsin possesses dual photosensory and photoisomerase functions, previously thought to be a unique feature of invertebrate rhabdomeric photopigments. In cultured cells that normally do not respond to light, heterologous expression of mammalian melanopsin confers light sensitivity that can be restored by prior stimulation with appropriate wavelengths. Using three different physiological and behavioural assays we show that this in vitro property translates to in vivo melanopsin-dependent non-visual responses. We find that pre-stimulation with long wavelength light not only restores but enhances single unit responses of SCN neurons to 480 nm light, whereas the long-wavelength stimulus alone fails to elicit any response. Recordings in Opn4 mice confirm that melanopsin provides the main photosensory input to the SCN and furthermore demonstrate that melanopsin is required for response enhancement since this capacity is abolished in the knockout mouse. The efficiency of the light enhancement effect is wavelength, irradiance and duration dependent. Prior long-wavelength light exposure also enhances short-wavelength induced phase shifts of locomotor activity and pupillary constriction, consistent with the expression of a photoisomerase-like function in non-visual responses to light.