Glycogen synthase kinase 3 regulates photic signaling in the suprachiasmatic nucleus

التفاصيل البيبلوغرافية
العنوان: Glycogen synthase kinase 3 regulates photic signaling in the suprachiasmatic nucleus
المؤلفون: Jennifer A. Davis, Karen L. Gamble, Jodi R. Paul, Rita M. Cowell, Alex S. McKeown, Stacie K. Totsch, Timothy W. Kraft, Eric M. Mintz
المصدر: European Journal of Neuroscience. 45:1102-1110
بيانات النشر: Wiley, 2017.
سنة النشر: 2017
مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Light Signal Transduction, animal structures, Light, Photoperiod, Circadian clock, Action Potentials, Mice, Transgenic, macromolecular substances, Motor Activity, Biology, Inhibitory postsynaptic potential, Retina, Article, Tissue Culture Techniques, Glycogen Synthase Kinase 3, Mice, 03 medical and health sciences, 0302 clinical medicine, GSK-3, Circadian Clocks, Internal medicine, medicine, Animals, Premovement neuronal activity, Circadian rhythm, Neurons, Suprachiasmatic nucleus, Kinase, General Neuroscience, Adaptation, Physiological, Circadian Rhythm, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Light effects on circadian rhythm, Female, Suprachiasmatic Nucleus, sense organs, 030217 neurology & neurosurgery
الوصف: Glycogen synthase kinase 3 (GSK3) 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 GSK3 exhibits a rhythm across the 24h day. We have recently shown that GSK3 is capable of influencing both the molecular clock and SCN neuronal activity rhythms. However, it is not known whether GSK3 regulates the response to environmental cues such as light. The goal of the present study was to test the hypothesis that GSK3 activation mediates light-induced SCN excitability and photic entrainment. Immunofluorescence staining in the SCN of mice showed that late-night light exposure significantly increased GSK3 activity (decreased pGSK3β levels) 30-60 minutes after the light-pulse. Additionally, pharmacological inhibition of GSK3 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 GSK3 (GSK3-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 GSK3-KI mice was phase-advanced compared to WT, in both normal and light-exposed conditions. Finally, GSK3-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 GSK3 activation contributes to light-induced phase-resetting at both the neurophysiological and behavioral levels. This article is protected by copyright. All rights reserved.
تدمد: 0953-816X
DOI: 10.1111/ejn.13549
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37adf7ed718e3a4f7e4b38d3fd205fc1
https://doi.org/10.1111/ejn.13549
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....37adf7ed718e3a4f7e4b38d3fd205fc1
قاعدة البيانات: OpenAIRE
الوصف
تدمد:0953816X
DOI:10.1111/ejn.13549