Neural Circuitry, Behavioral Correlates and Genetic Organization of the Mammalian Circadian Clock

Abstract

Mammalian circadian rhythms are orchestrated by the suprachiasmatic nuclei (SCN) of the hypothalamus. The SCN are composed of circadian clock neurons but the mechanisms by which these neuronal oscillators encode circadian physiology are incompletely understood. The overall objective of this dissertation was to determine the genetic and molecular organization of the neural network within the SCN, and elucidate how the SCN interacts with the environment to produce measurable behavioral and physiological circadian rhythms. Using genetic knockouts, molecular reporters and behavioral analyses, this dissertation explores the relationship between circadian genes, the SCN neural network in which these genes are expressed, and finally the behavioral output that results from this network in mice and humans. Overall these results suggest that circadian genes and light act together to organize the mammalian SCN neural network, and thus affect behavioral and neurological phenotypes.