Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 50, Pages 12984-12995Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4253-06.2006
Keywords
Dexras1; MAPK; circadian; photic; entrainment; PACAP; suprachiasmatic
Categories
Funding
- NIMH NIH HHS [MH62335, R01 MH062335] Funding Source: Medline
- NINDS NIH HHS [NS47176, R01 NS047176] Funding Source: Medline
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The mammalian master clock, located in the suprachiasmatic nucleus ( SCN), is exquisitely sensitive to photic timing cues, but the key molecular events that sculpt both the phasing and magnitude of responsiveness are not understood. Here, we show that the Ras-like G-protein Dexras1 is a critical factor in these processes. Dexras1-deficient mice (dexras1-/-) exhibit a restructured nighttime phase response curve and a loss of gating to photic resetting during the day. Dexras1 affects the photic sensitivity by repressing or activating time-of-day-specific signaling pathways that regulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase ( MAPK). During the late night, Dexras1 limits the capacity of pituitary adenylate cyclase (PAC) activating peptide (PACAP)/PAC1 to affect ERK/MAPK, and in the early night, light-induced phase delays, which are mediated predominantly by NMDA receptors, are reduced as reported previously. Daytime photic phase advances are mediated by a novel signaling pathway that does not affect the SCN core but rather stimulates ERK/MAPK in the SCN shell and triggers downregulation of clock protein expression.
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