Identifying the photoreceptive inputs to the mammalian circadian system using transgenic and retinally degenerate mice

The endogenous circadian clock of mammals retains synchrony with the external light:dark cycle through ocular photoreceptors. To date the identity of the photoreceptors responsible for mediating this response is unknown. This review outlines attempts using transgenic mouse models to address this deficit. Mice bearing specific inherited lesions of both rod and cone photoreceptors retain circadian photosensitivity as assessed by photoentrainment of behavioural rhythms and the light-induced suppression of pineal melatonin. These findings indicate that as yet unidentified non-rod, non-cone ocular photoreceptors are capable of contributing to circadian light responses. Nevertheless, the possibility that circadian photosensitivity is the responsibility of multiple photoreceptor classes including both rod/cone and novel photopigments remains. There is some indirect evidence in favour of this hypothesis. A definitive resolution of this issue is likely to employ comparisons of circadian action spectra in wild type and retinally degenerate mice.