Circadian Responses to Light-Flash Exposure: Conceptualization and New Data Guiding Future Directions

Kwoon Y. Wong, Fabian-Xosé Fernandez

A growing number of studies document circadian phase-shifting after exposure to millisecond light flashes. When strung together by intervening periods of darkness, these stimuli evoke pacemaker responses rivaling or outmatching those created by steady luminance, suggesting that the circadian system's relationship to light can be contextualized outside the principle of simple dose-dependence. In the current review, we present a brief chronology of this work. We then develop a conceptual model around it that attempts to relate the circadian effects of flashes to a natural integrative process the pacemaker uses to intermittently sample the photic information available at dawn and dusk. Presumably, these snapshots are employed as building blocks in the construction of a coherent representation of twilight the pacemaker consults to orient the next day's physiology (in that way, flash-resetting of pacemaker rhythms might be less an example of a circadian visual illusion and more an example of the kinds of gestalt inferences that the image-forming system routinely makes when identifying objects within the visual field; i.e., closure). We conclude our review with a discussion on the role of cones in the pacemaker's twilight predictions, providing new electrophysiological data suggesting that classical photoreceptors-but not melanopsin-are necessary for millisecond, intermediate-intensity flash responses in ipRGCs (intrinsically photosensitive retinal ganglion cells). Future investigations are necessary to confirm this "Cone Sentinel Model" of circadian flash-integration and twilight-prediction, and to further define the contribution of cones vs. rods in transducing pacemaker flash signals.