THE ROLE OF MELANOPSIN IN THE REGULATION OF CIRCADIAN BEHAVIOR AND LIGHT RESPONSES UNDER A WIDE VARIETY OF LIGHT-DARK ENVIRONMENTS

Circadian photoentrainment, the alignment of biological rhythms with the light-dark environment, is necessary for proper physiological functions in virtually all organisms. Light is the strongest regulator of circadian rhythms, especially in mammals. There is still much to learn however, about how light regulates circadian rhythms. During my Ph.D. candidacy, I studied the effects of light on circadian rhythms and on the master biological clock, the suprachiasmatic nucleus (SCN), by using genetically modified mouse lines. More specifically, I studied the contribution of melanopsin, a light responsive protein in the retina, to circadian light responses. Light exposure at night is known to shift the phase of the circadian clock, as well as induce neural activity in the SCN. In chapter 2, I present and discuss my findings that light differentially activates cells in the SCN in a time-of-day (circa-dian) –dependent manner and found that melanopsin is especially important for SCN light responses during the early night. Irregular light schedules and extreme light-dark environments can lead to stress-related responses. Responses and recovery of circadian rhythms from the exposure irregular light schedules is discussed in chapter 3. Melanopsin plays a surprising role in these light responses. In chapter 4, I present my findings that both melanopsin and day length play important roles in circadian photoentrainment, especially when the light-dark environment changes as happens during trans- meridian travel. During these studies, I uncovered an unappreciated role for the acute effect of light on activity (masking) in re-adjusting circadian rhythms to these changes in light-dark environment. My work also uncovered the strong possibility that brain regions other than the SCN play an important role in circadian photoentrainment and in acute light response