The Role of Orexin in Non-Photic Phase Shifting

Abstract

The intergeniculate leaflet (IGL), a primarily visual structure, and its principal neuropeptide, neuropeptide Y (NPY), are essential for non-photic phase shifting. This creates a paradox: why is an inherently visual structure necessary for a non-visual process? Converging evidence suggests that the lateral hypothalamus and its orexin (OX) cells communicate and electrically activate IGL cells in vitro during non-photic manipulations. The most compelling evidence, however, comes from studying the diurnal grass rat – an animal model that has not been characterized in terms of basic non-photic behaviour and anatomy. Within the diurnal grass rat, active NPY cells have close appositions with OX fibers during sleep deprivation. Taken together, this thesis hypothesized that OX is one of the arousal signals that can activate the IGL and its NPYergic cells during non-photic phase shifting. To test this hypothesis, 2 experiments were conducted on male and female animals. Firstly, we tested whether an in vivo infusion of OX into the IGL activated a significant number of cells in Syrian hamsters. Our results indicate that OX activates a significant number of IGL cells. Experiment 2 evaluated whether c-Fos expression was induced in a significant number of IGL NPY-IR cells and if a significant proportion of active NPY cells have appositions with OX fibers in response to sleep deprivation in NPY-GFP mice. Our findings not only establish mice as a model organism in studying the effects of sleep deprivation, but we further corroborated the findings within the grass rat. Additional studies are needed to establish a cause-effect relationship between OX fibers and NPY cells during non-photic phase shifting.