CREB and Circadian Timing

Ohio State University Research Foundation -Do Not Use, Columbus OH

Investigators

Abstract

Lay abstract Daily, or circadian, rhythms of biochemistry, physiology and behavior are observed in a wide variety of organisms. In mammals, the capacity to generate an endogenous circadian rhythm is dependent upon a discrete ensemble of neurons referred to as the suprachiasmatic nuclei (SCN). The SCN, located deep within the brain, form a "biological clock" that is entrainable to external stimuli, such as light. Over the past several years, advances at the molecular and genetic level have revealed that SCN rhythmicity results from autoregulatory feedback loops of so-called "clock genes". Through as yet unidentified molecular events, these feedback loops couple to output pathways that in turn initiate circadian rhythms of physiology and behavior. Importantly, external stimuli, such as light, are thought to entrain the circadian clock by resetting these loops. The main goal of this study is to determine the cellular signaling events that mediate rhythmic gene expression in the SCN. Towards this end, mouse SCN tissue will be utilized to 1) identify intracellular signaling pathways activated by light, 2) determine how light-activated pathways affect rhythmic expression of core clock genes, and 3) determine how genetic feedback loops initiate events that drive output from the clock. An understanding of the molecular events that drive SCN rhythmicity should provide new insights into how circadian-controlled behaviors, such as the sleep-wake cycle, are regulated. Furthermore, given the commonality of signaling events thought to mediate long-term adaptive changes in nervous system physiology, the data collected and approaches used in this study should be of relevance to neurobiologists examining a wide array of behavioral processes.