Circadian rhythms of redox state and regulation of neuronal excitability in suprachiasmatic nucleus of rodents

Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day-night cycle. They are driven by the central circadian clock in the brain, the suprachiasmatic nucleus (SCN), where a genetic oscillator plays an essential role. Clock-gene transcription/translation is sensitive to metabolic (redox) change; however, energetic cycles manifest as circadian rhythms in protein oxidation have been reported in anucleate cells, where no transcription occurs. Whether the brain clock expresses redox cycles and how such metabolic oscillations might affect neuronal physiology are unknown. Here we show a self-sustained circadian rhythm of SCN redox state that requires the molecular clockwork. The redox oscillation determines the excitability of SCN neurons through a non-transcriptional mechanism: alterations in redox state rapidly (< 2 min) reverse membrane polarization of SCN neurons via changes in multiple K+ channels. The redox regulation of neuronal excitability gates the SCN sensitivity and response to entraining signals of light, by modulating Ca2+ signaling in response to excitatory neurotransmission, targeting on a ryanodine receptor–dependent intracellular Ca2+ store. Our study provides a novel pathway for the metabolic oscillator to engage in the organization with the central circadian clock; it couples the molecular clockwork and cellular energetics with membrane physiology, suggesting a basis for dynamic regulation of SCN excitability that is closely tied to metabolism.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular & Integrative Physi

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2012

Author dc:creator

• Wang, Tongfei

Contributors dc:contributor

• Gillette, Martha U.
• Chung, Hee Jung
• Cox, Charles L.
• Gillette, Rhanor
• Wang, Yingxiao

• circadian rhythm
• suprachiasmatic nucleus (SCN)
• redox
• excitability
• Ca2+
• phase shift

Statement dc:rights

• Copyright 2012 Tongfei Wang

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/34398

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/34398