Circadian modulation of photoreception: A study protocol

Daily variation in our physiology and behavior at the 24-hour scale are governed by two independent processes, an endogenous circadian rhythm and a sleep homeostat. Through the retinohypothalamic pathway, which carries information from the retina, the hypothalamus responds to light in order to synchronize the internal circadian rhythm to the external environment, rendering visual input an important circadian signal. The link between visual signals and the circadian system may be bi-directional, i.e., the sensitivity of the visual system to light may be modulated by the circadian clock itself. Building upon converging evidence for a of time-of day dependency in image-forming (e.g. luminance perception) and non image-forming functions (e.g. pupillary light response), we will disentangle circadian and homeostatic effects on early stages of visual processing in a pre-registered study. We will use the ultrashort sleep-wake schedule spanning 40 hours with healthy participants (n = 24) staying in a constant dim light environment, and providing repeated measures of ocular structures and functional mechanisms in 3-hour intervals. Our focus will be on assessing photoreceptor sensitivity using silent-substitution pupillometry, and characterising post-receptoral retinal mechanisms underlying luminance and color perception using psychophysical threshold measurements. To estimate circadian phase, we will collect circadian biomarkers, including salivary melatonin and core body temperature. This study will characterize the circadian and homeostatic influence on retinal mechanisms, informing how daily variations in physiology influence how we process light in the environment.