Role of the ipRGC Circadian Clock in Visual Perception

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PROJECT SUMMARY Circadian rhythms are biological changes that act over the course of the 24 hour day to allow animals to anticipate daily changes to their environment. These rhythms control many aspects of an animal’s physiology and behavior crucial for survival, including sleep/wake cycles, timing of food intake, body temperature, and hormone release, and their disruption leads to a variety of negative health outcomes. Circadian rhythms are set by molecular “clocks” contained within single cells in nearly every tissue of the body and are synchronized by the central pacemaker within the SCN to coordinate the timing of physiology and behavior across the day. Despite the huge number of biological processes under circadian control and increased awareness of the negative impacts of circadian disruption on human health, little is understood about how molecular clocks act within single cells throughout the body to control their function over the course of the day. One of the most predictable daily environmental changes is the light/dark cycle, which changes over several orders of magnitude from midday to midnight. Retinal neurons, which must anticipate and encode visual stimuli over this range, contain their own molecular clocks, and multiple visual behaviors are known to be under circadian control. The goal of this project is to use the retina as a model to understand how molecular clocks control cellular function to ultimately influence behavior. Contrast sensitivity and the pupillary light reflex (PLR) are two behaviors that are under circadian control. Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are major contributors to both of these behaviors and contain molecular clocks that oscillate throughout the day. Moreover, these cells can be manipulated with multiple genetic tools, making ipRGCs an excellent model for studying the impact of the molecular clocks of single cells to cell signaling and behavior. In Aim 1 we will determine whether the molecular clock of ipRGCs is necessary for proper PLR and contrast sensitivity. In Aim 2 we will determine how ipRGC cellular function is impacted by disruption of the molecular clock in ipRGCs. Collectively these results will provide insight into the impact of molecular clocks within single cells on cellular signaling and behavior.