Abstract
Circadian rhythms are 24-h cycles in physiology and behavior that occur in virtually all organisms. These processes are not simply driven by changes in the external environment as they persist under constant conditions, providing evidence for an internal biological clock. In mammals, this clock is located in the hypothalamic suprachiasmatic nuclei (SCN) and is based upon an intracellular mechanism composed of a transcriptional–translational feedback loop composed of a number of core clock genes. However, a clock is of no use unless it can be set to the correct time. The primary time cue for the molecular clock in the SCN is light detected by the eye. The photoreceptors involved in this process include the rods and cones that mediate vision, as well as the recently identified melanopsin-expressing photosensitive retinal ganglion cells (pRGCs). Light information is conveyed to the SCN via the retinohypothalamic tract, resulting in an intracellular signaling cascade which converges on cAMP-response elements in the promoters of several key clock genes. Over the last two decades a number of studies have investigated the transcriptional response of the SCN to light stimuli with the aim of further understanding these molecular signaling pathways. Here we provide an overview of these studies and provide protocols for studying the molecular responses to light in the SCN clock.
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References
Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941
Johnson CH, Golden SS (1999) Circadian programs in cyanobacteria: adaptiveness and mechanism. Annu Rev Microbiol 53:389–409
Ouyang Y, Andersson CR, Kondo T, Golden SS, Johnson CH (1998) Resonating circadian clocks enhance fitness in cyanobacteria. Proc Natl Acad Sci U S A 95:8660–8664
West AC, Bechtold DA (2015) The cost of circadian desynchrony: evidence, insights and open questions. Bioessays 37:777–788
DeCoursey PJ, Krulas JR, Mele G, Holley DC (1997) Circadian performance of suprachiasmatic nuclei (SCN)-lesioned antelope ground squirrels in a desert enclosure. Physiol Behav 62:1099–1108
Paranjpe DA, Sharma VK (2005) Evolution of temporal order in living organisms. J Circadian Rhythms 3:7
Weaver DR (1998) The suprachiasmatic nucleus: a 25-year retrospective. J Biol Rhythm 13:100–112
Moore RY, Eichler VB (1972) Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res 42:201–206
Stephan FK, Zucker I (1972) Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci U S A 69:1583–1586
Welsh DK, Logothetis DE, Meister M, Reppert SM (1995) Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms. Neuron 14:697–706
Ueda HR, Chen W, Adachi A, Wakamatsu H, Hayashi S, Takasugi T, Nagano M, Nakahama K, Suzuki Y, Sugano S et al (2002) A transcription factor response element for gene expression during circadian night. Nature 418:534–539
O'Neill JS, Maywood ES, Hastings MH (2013) Cellular mechanisms of circadian pacemaking: beyond transcriptional loops. Handb Exp Pharmacol 217:67–103
Balsalobre A, Damiola F, Schibler U (1998) A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 93:929–937
Dibner C, Schibler U, Albrecht U (2010) The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 72:517–549
Yoo SH, Yamazaki S, Lowrey PL, Shimomura K, Ko CH, Buhr ED, Siepka SM, Hong HK, Oh WJ, Yoo OJ et al (2004) PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci U S A 101:5339–5346
Duffield GE (2003) DNA microarray analyses of circadian timing: the genomic basis of biological time. J Neuroendocrinol 15:991–1002
Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ (2002) Extensive and divergent circadian gene expression in liver and heart. Nature 417:78–83
Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB (2014) A circadian gene expression atlas in mammals: implications for biology and medicine. Proc Natl Acad Sci U S A 111:16219–16224
Moore RY (1995) Organization of the mammalian circadian system. Ciba Found Symp 183:88–99; discussion 100–106
Foster RG, Provencio I, Hudson D, Fiske S, De Grip W, Menaker M (1991) Circadian photoreception in the retinally degenerate mouse (rd/rd). J Comp Physiol A 169:39–50
Nelson RJ, Zucker I (1981) Photoperiodic control of reproduction in olfactory-bulbectomized rats. Neuroendocrinology 32:266–271
Freedman MS, Lucas RJ, Soni B, von Schantz M, Munoz M, David-Gray Z, Foster R (1999) Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284:502–504
Lucas RJ, Freedman MS, Munoz M, Garcia-Fernandez JM, Foster RG (1999) Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science 284:505–507
Hattar S, Liao HW, Takao M, Berson DM, Yau KW (2002) Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295:1065–1070
Hughes S, Jagannath A, Rodgers J, Hankins MW, Peirson SN, Foster RG (2016) Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells. Eye 30:247–254
Hankins MW, Peirson SN, Foster RG (2008) Melanopsin: an exciting photopigment. Trends Neurosci 31:27–36
Panda S, Sato TK, Castrucci AM, Rollag MD, DeGrip WJ, Hogenesch JB, Provencio I, Kay SA (2002) Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science 298:2213–2216
Ruby NF, Brennan TJ, Xie X, Cao V, Franken P, Heller HC, O'Hara BF (2002) Role of melanopsin in circadian responses to light. Science 298:2211–2213
Hattar S, Lucas RJ, Mrosovsky N, Thompson S, Douglas RH, Hankins MW, Lem J, Biel M, Hofmann F, Foster RG et al (2003) Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 424:76–81
Lucas RJ, Peirson SN, Berson DM, Brown TM, Cooper HM, Czeisler CA, Figueiro MG, Gamlin PD, Lockley SW, O'Hagan JB et al (2014) Measuring and using light in the melanopsin age. Trends Neurosci 37:1–9
Schmidt TM, Chen SK, Hattar S (2011) Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci 34:572–580
Baver SB, Pickard GE, Sollars PJ, Pickard GE (2008) Two types of melanopsin retinal ganglion cell differentially innervate the hypothalamic suprachiasmatic nucleus and the olivary pretectal nucleus. Eur J Neurosci 27:1763–1770
Berson DM, Dunn FA, Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science 295:1070–1073
Hattar S, Kumar M, Park A, Tong P, Tung J, Yau KW, Berson DM (2006) Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol 497:326–349
Guler AD, Ecker JL, Lall GS, Haq S, Altimus CM, Liao HW, Barnard AR, Cahill H, Badea TC, Zhao H et al (2008) Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision. Nature 453:102–105
Ding JM, Chen D, Weber ET, Faiman LE, Rea MA, Gillette MU (1994) Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. Science 266:1713–1717
Hannibal J, Moller M, Ottersen OP, Fahrenkrug J (2000) PACAP and glutamate are co-stored in the retinohypothalamic tract. J Comp Neurol 418:147–155
Hughes S, Jagannath A, Hankins MW, Foster RG, Peirson SN (2015) Photic regulation of clock systems. Methods Enzymol 552:125–143
Colwell CS (2011) Linking neural activity and molecular oscillations in the SCN. Nat Rev Neurosci 12:553–569
Gau D, Lemberger T, von Gall C, Kretz O, Le Minh N, Gass P, Schmid W, Schibler U, Korf HW, Schutz G (2002) Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock. Neuron 34:245–253
Ginty DD, Kornhauser JM, Thompson MA, Bading H, Mayo KE, Takahashi JS, Greenberg ME (1993) Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. Science 260:238–241
Meijer JH, Schwartz WJ (2003) In search of the pathways for light-induced pacemaker resetting in the suprachiasmatic nucleus. J Biol Rhythm 18:235–249
Jagannath A, Butler R, Godinho SI, Couch Y, Brown LA, Vasudevan SR, Flanagan KC, Anthony D, Churchill GC, Wood MJ et al (2013) The CRTC1-SIK1 pathway regulates entrainment of the circadian clock. Cell 154:1100–1111
Sakamoto K, Norona FE, Alzate-Correa D, Scarberry D, Hoyt KR, Obrietan K (2013) Clock and light regulation of the CREB coactivator CRTC1 in the suprachiasmatic circadian clock. J Neurosci 33:9021–9027
Nadon R, Shoemaker J (2002) Statistical issues with microarrays: processing and analysis. Trends Genet 18:265–271
Peirson SN, Butler JN, Duffield GE, Takher S, Sharma P, Foster RG (2006) Comparison of clock gene expression in SCN, retina, heart, and liver of mice. Biochem Biophys Res Commun 351:800–807
Pilorz V, Tam SK, Hughes S, Pothecary CA, Jagannath A, Hankins MW, Bannerman DM, Lightman SL, Vyazovskiy VV, Nolan PM et al (2016) Melanopsin regulates both sleep-promoting and arousal-promoting responses to light. PLoS Biol 14:e1002482
Peirson SN, Butler JN (2007) RNA extraction from mammalian tissues. Methods Mol Biol 362:315–327
Peirson SN, Butler JN (2007) Quantitative polymerase chain reaction. Methods Mol Biol 362:349–362
Albrecht U, Foster RG (2002) Placing ocular mutants into a functional context: a chronobiological approach. Methods 28:465–477
Foster RG (2002) Keeping an eye on the time: the Cogan Lecture. Invest Ophthalmol Vis Sci 43:1286–1298
Jud C, Schmutz I, Hampp G, Oster H, Albrecht U (2005) A guideline for analyzing circadian wheel-running behavior in rodents under different lighting conditions. Biol Proc Online 7:101–116
Peirson SN, Thompson S, Hankins MW, Foster RG (2005) Mammalian photoentrainment: results, methods, and approaches. Methods Enzymol 393:697–726
Meijer JH, Schaap J, Watanabe K, Albus H (1997) Multiunit activity recordings in the suprachiasmatic nuclei: in vivo versus in vitro models. Brain Res 753:322–327
Meijer JH, Watanabe K, Schaap J, Albus H, Detari L (1998) Light responsiveness of the suprachiasmatic nucleus: long-term multiunit and single-unit recordings in freely moving rats. J Neurosci 18:9078–9087
Kornhauser JM, Mayo KE, Takahashi JS (1996) Light, immediate-early genes, and circadian rhythms. Behav Genet 26:221–240
Albrecht U, Sun ZS, Eichele G, Lee CC (1997) A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light. Cell 91:1055–1064
Honma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, Kato Y, Honma K (2002) Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature 419:841–844
Shearman LP, Zylka MJ, Weaver DR, Kolakowski LF Jr, Reppert SM (1997) Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei. Neuron 19:1261–1269
Shigeyoshi Y, Taguchi K, Yamamoto S, Takekida S, Yan L, Tei H, Moriya T, Shibata S, Loros JJ, Dunlap JC et al (1997) Light-induced resetting of a mammalian circadian clock is associated with rapid induction of the mPer1 transcript. Cell 91:1043–1053
Sun ZS, Albrecht U, Zhuchenko O, Bailey J, Eichele G, Lee CC (1997) RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell 90:1003–1011
Lin JT, Kornhauser JM, Singh NP, Mayo KE, Takahashi JS (1997) Visual sensitivities of nur77 (NGFI-B) and zif268 (NGFI-A) induction in the suprachiasmatic nucleus are dissociated from c-fos induction and behavioral phase-shifting responses. Brain Res Mol Brain Res 46:303–310
Morris ME, Viswanathan N, Kuhlman S, Davis FC, Weitz CJ (1998) A screen for genes induced in the suprachiasmatic nucleus by light. Science 279:1544–1547
Araki R, Nakahara M, Fukumura R, Takahashi H, Mori K, Umeda N, Sujino M, Inouye ST, Abe M (2006) Identification of genes that express in response to light exposure and express rhythmically in a circadian manner in the mouse suprachiasmatic nucleus. Brain Res 1098:9–18
Porterfield VM, Piontkivska H, Mintz EM (2007) Identification of novel light-induced genes in the suprachiasmatic nucleus. BMC Neurosci 8:98
Cheng HY, Papp JW, Varlamova O, Dziema H, Russell B, Curfman JP, Nakazawa T, Shimizu K, Okamura H, Impey S et al (2007) microRNA modulation of circadian-clock period and entrainment. Neuron 54:813–829
Porterfield VM, Mintz EM (2009) Temporal patterns of light-induced immediate-early gene expression in the suprachiasmatic nucleus. Neurosci Lett 463:70–73
Zhu H, Vadigepalli R, Rafferty R, Gonye GE, Weaver DR, Schwaber JS (2012) Integrative gene regulatory network analysis reveals light-induced regional gene expression phase shift programs in the mouse suprachiasmatic nucleus. PLoS One 7:e37833
Hannibal J, Ding JM, Chen D, Fahrenkrug J, Larsen PJ, Gillette MU, Mikkelsen JD (1997) Pituitary adenylate cyclase-activating peptide (PACAP) in the retinohypothalamic tract: a potential daytime regulator of the biological clock. J Neurosci 17:2637–2644
Mieda M, Ono D, Hasegawa E, Okamoto H, Honma K, Honma S, Sakurai T (2015) Cellular clocks in AVP neurons of the SCN are critical for interneuronal coupling regulating circadian behavior rhythm. Neuron 85:1103–1116
Jones JR, Tackenberg MC, McMahon DG (2015) Manipulating circadian clock neuron firing rate resets molecular circadian rhythms and behavior. Nat Neurosci 18:373–375
VanDunk C, Hunter LA, Gray PA (2011) Development, maturation, and necessity of transcription factors in the mouse suprachiasmatic nucleus. J Neurosci 31:6457–6467
Mori K, Miyazato M, Ida T, Murakami N, Serino R, Ueta Y, Kojima M, Kangawa K (2005) Identification of neuromedin S and its possible role in the mammalian circadian oscillator system. EMBO J 24:325–335
Cheng MY, Bullock CM, Li C, Lee AG, Bermak JC, Belluzzi J, Weaver DR, Leslie FM, Zhou QY (2002) Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature 417:405–410
Doi M, Ishida A, Miyake A, Sato M, Komatsu R, Yamazaki F, Kimura I, Tsuchiya S, Kori H, Seo K et al (2011) Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus. Nat Commun 2:327
Hong HK, Chong JL, Song W, Song EJ, Jyawook AA, Schook AC, Ko CH, Takahashi JS (2007) Inducible and reversible Clock gene expression in brain using the tTA system for the study of circadian behavior. PLoS Genet 3:e33
Husse J, Zhou X, Shostak A, Oster H, Eichele G (2011) Synaptotagmin10-Cre, a driver to disrupt clock genes in the SCN. J Biol Rhythms 26:379–389
Reed HE, Meyer-Spasche A, Cutler DJ, Coen CW, Piggins HD (2001) Vasoactive intestinal polypeptide (VIP) phase-shifts the rat suprachiasmatic nucleus clock in vitro. Eur J Neurosci 13:839–843
Harmar AJ, Marston HM, Shen S, Spratt C, West KM, Sheward WJ, Morrison CF, Dorin JR, Piggins HD, Reubi JC et al (2002) The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei. Cell 109:497–508
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Dannerfjord, A.A., Brown, L.A., Foster, R.G., Peirson, S.N. (2021). Light Input to the Mammalian Circadian Clock. In: Brown, S.A. (eds) Circadian Clocks. Methods in Molecular Biology, vol 2130. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0381-9_18
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DOI: https://doi.org/10.1007/978-1-0716-0381-9_18
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