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Glycogen synthase kinase 3 regulates photic signaling in the suprachiasmatic nucleus
Author(s) -
Paul Jodi R.,
McKeown Alex S.,
Davis Jennifer A.,
Totsch Stacie K.,
Mintz Eric M.,
Kraft Timothy W.,
Cowell Rita M.,
Gamble Karen L.
Publication year - 2017
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13549
Subject(s) - suprachiasmatic nucleus , gsk 3 , circadian rhythm , endocrinology , biology , medicine , light effects on circadian rhythm , gsk3b , glycogen synthase , premovement neuronal activity , neuroscience , circadian clock , microbiology and biotechnology , phosphorylation , chemistry , glycogen
Glycogen synthase kinase 3 ( GSK 3) is a serine‐threonine kinase that regulates mammalian circadian rhythms at the behavioral, molecular and neurophysiological levels. In the central circadian pacemaker, the suprachiasmatic nucleus ( SCN ), inhibitory phosphorylation of GSK 3 exhibits a rhythm across the 24 h day. We have recently shown that GSK 3 is capable of influencing both the molecular clock and SCN neuronal activity rhythms. However, it is not known whether GSK 3 regulates the response to environmental cues such as light. The goal of this study was to test the hypothesis that GSK 3 activation mediates light‐induced SCN excitability and photic entrainment. Immunofluorescence staining in the SCN of mice showed that late‐night light exposure significantly increased GSK 3 activity (decreased pGSK 3β levels) 30–60 min after the light‐pulse. In addition, pharmacological inhibition of GSK 3 blocked the expected light‐induced excitability in SCN neurons; however, this effect was not associated with changes in resting membrane potential or input resistance. Behaviorally, mice with constitutively active GSK 3 ( GSK 3‐ KI ) re‐entrained to a 6‐h phase advance in the light‐dark cycle in significantly fewer days than WT control animals. Furthermore, the behavioral and SCN neuronal activity of GSK 3‐ KI mice was phase‐advanced compared to WT , in both normal and light‐exposed conditions. Finally, GSK 3‐ KI mice exhibited normal negative‐masking behavior and electroretinographic responses to light, suggesting that the enhanced photic entrainment is not due to an overall increased sensitivity to light in these animals. Taken together, these results provide strong evidence that GSK 3 activation contributes to light‐induced phase‐resetting at both the neurophysiological and behavioral levels.