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Contribution of serotonin 2C receptors to the regulation of circadian rhythm entrainment


Many aspects of physiology and behavior are driven by circadian rhythms that oscillate with a period of roughly twenty-four hours. These circadian rhythms are evolutionarily adapted to entrain to light and to food availability. Light-entrainable circadian rhythms are driven by a master pacemaker that resides in the suprachiasmatic nucleus (SCN), while food-entrainable circadian rhythms are driven by a separate food-entrainable oscillator (FEO), the neural basis of which remains unclear. Serotonin systems have been implicated in the regulation of circadian rhythms. However, the challenge in elucidating the mechanisms by which serotonin regulates circadian rhythms lay in the fact that serotonin exerts its effects via fourteen different serotonin receptors. This thesis investigates the role of serotonin2C receptors (5-HT2CRs) in the regulation of both light- and food-entrainable circadian rhythms, using a combination of genetics, behavioral assessment, and anatomical analysis. We present data that indicates an important contribution of 5-HT2CRs to the facilitation of light entrainable circadian rhythms, and to the gating of food-entrainable circadian rhythms.

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