Distinct ipRGC subpopulations mediate light’s acute and circadian effects on body temperature and sleep

Light, whether natural or artificial, affects our everyday lives in several ways. Exposure to light impacts on our health and well-being. It plays a crucial but indirect role in helping to align our internal body clock with the 24-hour cycle of day and night, and a burst of bright light in the middle of the night can wake us up from sleep. Decades of research have revealed the circuitry that controls the indirect effects of light on the body's internal clock. A tiny set of cells in the base of the brain called the suprachiasmatic nucleus (SCN for short) generates the body’s daily or “circadian” rhythm. A small group of nerve cells in the retina of the eye called intrinsically photosensitive retinal ganglion cells (ipRGCs) connect with the SCN. These ipRGCs relay information about light to the SCN to ensure that daily rhythms happen at the appropriate times of day. But scientists do not yet know if the same brain circuits regulate the direct effects of light on alertness. Mice are often used in studies of circadian rhythms but, unlike humans, mice are normally active at night and sleep throughout the day. This means that a burst of bright light in the middle of the night causes mice to become less alert. Now, in experiments with mice, Rupp et al. show there are two separate circuits from the retina to the brain that influence wakefulness. In the experiments, some mice were genetically engineered to only have ipRGCs that connect with the SCN and to lack those that connect with other brain areas. These mice lived in cages with a normal day/night cycle and their body temperature and sleep-related brain activity were monitored as Rupp et al. sporadically exposed them to bright light at night. These mice continued their normal routines and were unaffected by the bursts of light. In a second set of experiments, ipRGCs that do not connect with the SCN were activated in other mice. This caused an immediate and sustained drop in the body temperature of the mice, which is linked to them becoming less alert. The experiments suggest that the circuit that connects ipRGCs to the SCN to align the body’s circadian rhythm with light does not control the direct effect of light on wakefulness. Instead, a separate circuit that extends from ipRGCs to an unknown part of the brain area influences wakefulness. Better understanding this second circuit could allow scientists to develop ways to keep people like emergency personnel or overnight shift workers awake and alert at night while avoiding harmful disruptions to their circadian rhythms.