The proposed experiments are designed to develop an understanding of the functional neuroanatomy involved in the serotonergic modulation of the circadian timing system. Neuroanatomy of the circadian timing system appears well conserved between species, and it is expected that information gathered in these hamster experiments is applicable to humans. Abnormalities in circadian rhythmicity are believed to be the underlying cause of several depressive mental illnesses, including seasonal affective disorder. Thus, a comprehensive understanding of the circadian system will allow for the development of a more effective treatment of depression. The serotonergic projection to the circadian timing system is known to originate in the raphe region of the mesencephalon. However, studies investigating the precise nucleus of origin have been both contradictory and unsatisfactory in their anatomical descriptions. Recent evidence from our laboratory leads us to believe the median raphe nucleus provides the serotonergic innervation to this system. Retrograde and anterograde tract tracing techniques will be utilized to confirm this hypothesis and determine to what extent single raphe cells bifurcate to innervate multiple targets in the circadian system. In addition, the functional significance of the projection in the modulation of circadian rhythms will be investigated. The effects of general serotonin manipulation on circadian rhythms have been well documented. This proposal aims to establish that the serotonergic projection from the median raphe is responsible for these effects. Ablation and stimulation techniques applied specifically to the median raphe will be used to investigate the role of this nucleus in circadian rhythm modulation.
