Exquisite light sensitivity of Drosophila melanogaster cryptochrome

Drosophila melanogaster shows exquisite light sensitivity for modulation of circadian functions in vivo, yet the activities of the Drosophila circadian photopigment cryptochrome (CRY) have only been observed at high light levels. We studied intensity/duration parameters for light pulse induced circadian phase shifts under dim light conditions in vivo. Flies show far greater light sensitivity than previously appreciated, and show a surprising sensitivity increase with pulse duration, implying a process of photic integration active up to at least 6 hours. The CRY target timeless (TIM) shows dim light dependent degradation in circadian pacemaker neurons that parallels phase shift amplitude, indicating that integration occurs at this step, with the strongest effect in a single identified pacemaker neuron. Our findings indicate that CRY compensates for limited light sensitivity in vivo by photon integration over extraordinarily long times, and point to select circadian pacemaker neurons as having important roles.
Author Summary We investigate the paradox that fruit flies show exquisite light sensitivity for day/night circadian clock functions, yet the circadian photoreceptor cryptochrome (CRY) responds only to very high light levels in assays requiring immediate responses. Our in vivo behavioral assays are unique in that we expose flies to dim and limiting levels of light. We find that CRY integrates photons efficiently over time periods of at least six hours, with light sensitivity unexpectedly increasing with duration of light exposure. This contrasts with image-forming responses that occur on millisecond time scales in Drosophila. We show that light dependent degradation of the CRY target timeless (TIM) occurs at limiting light levels, closely paralleling behavioral effects, in the circadian pacemaker neurons. One of these neurons shows particularly strong light sensitivity, and a particularly strong temporal integration effect. We have thus identified the precise step at which temporal integration is functioning. The structurally unrelated vertebrate circadian photoreceptor melanopsin also shows the ability to integrate photons over time, though not to the extent of Drosophila CRY. We thus conclude that temporal integration is a universal mechanism to enhance photosensitivity of non-visual photopigments.