Are the Benefits of Bright Light Therapy Dependent on the Activity of the SCN?

Mood disorders represent a major toll on the health of people, severely deteriorating the quality of life, with seasonal affective disorder (SAD) being such an example. As a first line of treatment for SAD, bright light is administered. Light therapy has been shown to affect mood in humans. Meanwhile, the involvement of the circadian clock on the molecular mechanisms that translate positive effects of light in mood remain poorly understood. Using mice as an animal model, our lab has identified clock gene Per1 as a component required to mediate the benefits of light. Per1 deletion in the lateral habenula, a region involved in controlling mood-related behaviors, led to suppression of the valuable effects of light applied at zeitgeber time (ZT) 22. A light pulse at ZT22 (analogous to bright light therapy) is associated with a phase advance which has been proven to ameliorate mood in depressive patients. Hence, we are interested in seeing if mice who do not present this advance still profit from the light pulse. To that extend, we will be using mice that have a Per1 knock-out in the suprachiasmatic nuclei (SCN). While their locomotor activities will be recorded, a light pulse will be applied at ZT14 (phase delay) and ZT22 (phase advance) and compared to a control group. We hypothesize that Per1 knock-out group will not show any phase advance. Both groups will then undergo the behavioral experiments of Forced Swim Test (FST), sucrose preference test (SPT) and the O-maze test. These results will be consolidated at the biochemical level by looking at changes in the rate limiting enzymes involved in the dopamine metabolism, tyrosine hydroxylase and monoamine oxidase. Taken together, this experimental design can help us conclude if the light induction of Per1 in the lateral habenula is sufficient for the beneficial effects of light or whether phase advances mediated by the SCN are necessary.