Cholinergic Regulation of Circadian Rhythms in the SCN: Characterization of Signaling Mechanisms and the Role of Intracellular Calcium in the Directionality of Clock Resetting

120 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2001.This study shows that stimulus-specific intracellular Ca2+ (Ca2+i) release controls the direction of clock resetting. Direct activation of the InsP3-induced Ca2+ i release (IICR) mimics cholinergic phase advance, while InsP3 , but not ryanodine, receptor antagonists block it. In contrast, selective activation of CICR with ryanodine results in glutamate-like delay. Ca 2+ imaging using multiphoton microscopy revealed signal-specific differences in Ca2+ transients. Cholinergic-stimulated Ca2+ transients are localized to the microdomains in the cytoplasm, whereas glutamate-induced Ca2+ transients are predominantly uniform across the cytosol and nucleus. Thus, the direction of clock resetting is determined by differential Ca2+i release that is likely to result in activation of spatially restricted Ca2+-dependent effector proteins.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD