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

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular and Integrative Physiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Artinian, Liana

Contributors dc:contributor

• Gillette, Martha U.

• Biology, Neuroscience

Language dc:language

eng

Identifier

(MiAaPQ)AAI3017015

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/87212