REVIEW ■ : The Suprachiasmatic Nucleus: A Circadian Oscillator

Abstract

The suprachiasmatic nucleus (SCN) is considered to be a circadian oscillator that regulates a set of phys iological aspects of behavior, including sleep-wakefulness and hormone release in mammalian species. In this review, we describe recent research that has begun to reveal the functional organization of the SCN. The SCN, which consists of a bilateral pair of tiny nuclei located just above the optic chiasm, contains several kinds of peptidergic neurons, but vasoactive intestinal peptide (VIP), arginine vasopressin (AVP), and somatostatin (SOM) neurons are the main components. VIP neurons and AVP neurons show distinctly different locations in the SCN; the former are found in the ventrolateral portion, whereas the latter are localized in the dorsomedial portion. VIP neurons receive all neuronal inputs from other regions of the CNS, such as those evoked by photic stimulation via the retinal ganglion cells and those relayed by 5HT inner vation from the raphe nuclei. VIP neurons relay their information to other kinds of neurons in the SCN, such as AVP and SOM neurons. VIP neurons, thus, may play a significant role in entrainment of circadian rhythm. VIP, AVP, SOM, and their mRNAs show rhythmic fluctuations that are predicted by this model; VIP and its mRNA show diurnal variation under the influence of photic stimulation, whereas AVP, SOM, and their mRNAs show endogenous rhythms. Immediate early genes (lEGs), such as c-fos mRNA, are also expressed in VIP neurons in the SCN, and IEG expression in the cells appears to be modified by photic stimuli. Together with transplantation studies showing that exogenous SCN tissue tends to restore circadian rhythm in arrhythmic animals, these results are beginning to clarify the function of the SCN in setting, maintaining, and resetting the biological clock. NEUROSCIENTIST 3:215-225, 1997

Keywords

KEY WORDS Suprachiasmatic nucleus Vasoactive intestinal peptide (VIP)Vasopressin Immunocytochemistry In situ hybridization Rat

Get full access to this article

View all access options for this article.

References

Ibuka N. , Kawamura H. Loss of circadian sleep-wakefulness cycle in the rat by suprachiasmatic nucleus lesion. Brain Res 1975;96: 76-81.

Moore RY , Eichler VB Less of a circadian adrenal corticosterone rhythm following suprachiasmatic lesion in the rat. Brain Res 1972;42:201-206.

Sawaki Y. , Nihonmatsu I. , Kawamura H. Transplantation of the neonatal suprachiasmatic nucleus into rats with complete bilateral suprachiasmtaic lesions. Neurosci Res 1984;1:67-72.

Lehman MN , Silver R. , Gladston WR , et al. Circadian rhythmicity restored by neuronal transplant: immunocytochemical charactenzation of the graft and its integration with the host brain. J Neurosci 1987;7:1626-1638.

Ralph MR , Foster RG , Davis FC , et al. Transplanted suprachiasmatic nucleus determines circadian period . Science 1990;247:975-978.

Moore RY , Lenn NJ A retinohypothalamic projection in the rat. J Comp Neurol 1972;146:1-14.

Morin LP , Johnson RF , Moore RY Two brain nuclei controlling circadian rhythms are identified by GFAP immunoreactivity in hamsters and rats. Neurosci Lett 1989;99:55-60.

Okamura H. , Abitbol M. , Julien J-F, et al. Neurons containing messenger RNA encoding glutamate decarboxylase in rat hypothalamus demonstrated by in situ hybndizarion, with special emphasis on cell groups in medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus. Neuroscience 1990;39: 675-699.

Okamura H. , Takahashi Y. , Terubayashi H. , et al. VIP-like immunoreactive neurons and retinal projections in the rat suprachiasmatic nucleus. Biomed Res 1987 ;8:253-262.

10.

Okamura H. , Tominaga K. , Ban Y. , et al. Morphological survey of the suprachiasmatic nucleus in slice culture using roller tube method: 1. architecture of the suprachiasmatic nucleus in vitro. Acta Histochem Cytochem 1994;27:159-169.

11.

Okamura H. , Tommaga K. , Ban Y. , et al. Morphological survey of the suprachiasmatic nucleus in slice culture using roller tube method: 2. peptidergic neurons. Acta Histochem Cytochem 1994;27:171-179.

12.

van den Pol A. The hypothalamic suprachiasmatic nucleus of rat: intrinsic anatomy. J Comp Neurol 1980;191:661-702.

13.

van den Pol A. , Tsujimoto KL Neurotransmitters of the hypothalamic suprachiasmatic nucleus: immunocytochemical analysis of 25 neuronal antigens. Neuroscience 1985;15:1049-1086.

14.

Ibata Y. , Tanaka M. , Ichitani Y. , et al. Neuronal interaction between VIP and vasopressm neurons in the rat suprachiasmatic nucleus. Neuroreport 1993 ;4:128-130.

15.

Tanaka M. , Okamura H. , Matsuda T. , et al. Somatostatin neurons from a distinct peptidergic neuronal group in the rat suprachiasmatic nucleus: a double labeling in situ hybndization study. Neurosci Lett 1996;215:119-122.

16.

Ibata Y. , Takahashi Y. , Okamura H. , et al. Vasoactive intestinal peptide (VIP)-like immunoreactive neurons located in the rat suprachiasmatic nucleus receive a direct retinal projection. Neurosci Lett 1989;97:1-5.

17.

Kiss J. , Leranth CS , Halasz B. Serotonergic endings on VIP-neurons in the suprachiasmatic nucleus and on ACTH-neurons in the arcuate nucleus of the rat hypothalamus. A combination of high resolution autoradiography and electron microscopic immunocytochemistry. Neurosci Lett 1984;44:119-124.

18.

Hisano S. , Chikamon-Aoyama M. , Katoh S. , et al. Suprachiasmatic nucleus neurons immunoreactive for vasoactive intestinal polypeptide have synaptic contacts with axons immunoreactive for neuropeptide Y: an immunoelectron microscopic study in the rat. Neurosci Lett 1988;88:145-150.

19.

Card JP , Moore RY Ventral lateral gemculate nucleus efferents to the rat suprachiasmatic nucleus exhibit avian pancreatic polypeptide-like immunoreactivity. J Comp Neurol 1982;206:390-396.

20.

Tanaka M. , Ichitani Y. , Okamura H. , et al. The direct retinal projection to VIP neuronal elements in the rat SCN. Brain Res Bull 1993;31:637-640.

21.

Ding JM , Chen D. , Webber ET , et al. Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. Science 1994;266:1713-1717.

22.

Takeuchi Y. , Takashima M. , Katoh Y. , et al. N-methyl-D-aspartate, quisqualate and kamate receptors are all involved in transmission of photic stimulation in the suprachiasmatic nucleus in rat. Brain Res 1991;563:127-131.

23.

Takatsuji K. , Miguel-Hidalgo J-J. , Tohyama M. Substance P-immunoreactive innervation from the retina to the suprachiasmatic nucleus in the rat. Brain Res 1991;568:223-229.

24.

Watts AG , Swanson LW , Sanchez-Watts G. Efferent projections of the suprachiasmatic nucleus: I. studies using anterograde transport of phaseolus vulgans leucoagglutinin in the rat. J Comp Neurol 1987;258:204-229.

25.

Watts AG , Swanson LW Efferent projections of the suprachiasmatic nucleus: II. studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat. J Comp Neurol 1987;258:230-252.

26.

Vrang N. , Larsen PJ , Mikkelsen JD Direct projection from the suprachiasmatic nucleus to hypophysiotrophic corticotrophin-releasing factor immunoreactive cells in the paraventncular nucleus of the hypothalamus demonstrated by means of phaseolus vulgans-leucoagglutmm tract tracing. Brain Res 1995;684:61-69.

27.

van der Beek EM , Weigant VM , van der Donk HA , et al. Lesions of the suprachiasmatic nucleus indicate the presence of a direct vasoactive intestinal polypeptide-containing projection to gonadotrophin-releasing hormone neurons in the female rat. J Neuroendocnnol 1993;5:137-144.

28.

Moore RY , Klein DC Visual pathways and the central neural control of a circadian rhythm in pineal serotonin N-acetyltransferase activity. Brain Res 1974;71:17-33.

29.

Klein DC , Weller JL Indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase . Science 1970;169:1093-1095.

30.

Reppert SM , Weaver DR , Ebisawa T. Cloning and charactenzation of mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 1994;13:1177-1185.

31.

Kilduff TS , Landel HB , Nagy GS , et al. Melatonin influences Fos expression in the rat suprachiasmatic nucleus. Mol Brain Res 1992;16:47-56.

32.

Petrie K. , Conaglen JV , Thompson L. , et al. Effects of melatonin on jet lag after long haul flights. Br Med J 1989;298:705-707.

33.

Palm L. , Blennow G. , Wetterberg L. Correction of non-24 hour sleep/wake cycle by melatonin in a blind retarded boy. Ann Neurol 1991;29:336-339.

34.

Kawakami F. , Okamura H. , Fukui K. , et al. The influence of serotonergic inputs on peptide neurons in the rat suprachiasmatic nucleus : an immunocytochemical study. Neurosci Lett 1985;61: 273-277.

35.

Kawakami F. , Okamura H. , Tamada Y. , et al. Changes in vasoactive intestinal peptide mRNA levels in the rat suprachiasmatic nucleus following p-chlorophenylalanine (PCPA) treatment under light/ dark conditions. Neurosci Lett 1995;200:171-174.

36.

Takahashi Y. , Okamura H. , Yanaihara N. , et al. Vasoactive intestmal peptide immunoreactive neurons in the rat suprachiasmatic nucleus demonstrate diurnal vanation. Brain Res 1989;497:374-377.

37.

Okamoto S. , Okamura H. , Miyake M. , et al. A diurnal variation of vasoactive intestinal peptide (VIP) mRNA under a daily light-dark cycle in the rat suprachiasmatic nucleus. Histochemistry 1991; 95:525-528.

38.

Okamura H. , Kawakami F. , Tamada Y. , et al. Circadian change of VIP mRNA in the rat suprachiasmatic nucleus following p-chlorophenylalanme (PCPA) treatment in constant darkness. Mol Brain Res 1995;29:358-364.

39.

Uhl GR , Reppert SM Suprachiasmatic nucleus vasopressm messenger RNA: circadian variation in Normal and Brattleboro rats. Science 1986 ;232:390-393.

40.

Fukuhara C. , Shinohara K. , Tominaga K. , et al. Endogenous circadian rhythmicity of somatostarin like-immunoreactivity in the rat suprachiasmatic nucleus. Brain Res 1993;606:28-35.

41.

Nishiwalo T. , Okamura H. , Kanemasa K. , et al. Differences of somatostatm mRNA in the rat suprachiasmatic nucleus under light-dark and constant dark conditions: an analysis by in situ hybridization. Neurosci Lett 1995;197:231-234.

42.

Hunt SP , Pini A. , Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation . Nature 1987;328: 632-634.

43.

Neumann-Haeielin T. , Wiessner C. , Vogel P. , et al. Differential expression of immediate early genes c-fos, c-jun, jun-B and NGFI-B in the rat brain following transient forebrain ischemia. J Cereb Blood Flow Metab 1994;14:206-216.

44.

Rusak B. , Robertson HA , Wisden W. , et al. Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus. Science 1990;248:1237-1240.

45.

Sutin EL , Kilduff TS Circadian and light induced expression of immediate early gene mRNA in the rat suprachiasmatic nucleus. Mol Brain Res 1992;15:281-290.

46.

Sumova A. , Trávníčková Z. , Peters R. , et al. The rat suprachiasmatic nucleus is a clock for all seasons. Proc Natl Acad Sci U S A 1995; 92:7754-7758.

47.

Golombek DA , Ralph MR Circadian responses to light: the calmodulin connection. Neurosci Lett 1995,192:101-104.

48.

Aguilar-Roblero R. , Garcia-Hernandez F. , Aguilar R. , et al. Suprachiasmatic nucleus transplants function as an endogenous oscillator only in constant darkness. Neurosci Lett 1986;69:47-52.

49.

Silver R. , LeSauter J. Circadian rhythms 5. What do suprachiasmatic nucleus transplants do ? Brain Res Rev 1993;18:315-333.

50.

Konopka RJ , Benzer S.

Clock mutant of Drosophila melanogaster

Proc Natl Acad Sci U S A 1971;68:2112-2116.

51.

Mclung CR , Fox BA , Dunlap JC The neurospora clock gene frequency shares requence element with the Drosophila clock gene period. Nature 1989;339:558-562.

52.

Kondo T. , Tsinoremas NF , Goldman SS , et al. Circadian clock mutants of cyanobactena. Science 1994;266:1233-1236

53.

Sehgal A. , Price JL , Man B. , et al. Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. Science 1994 ;263:1603-1606.

54.

Myers MP , Wager-Smith K. , Wesley CS , et al. Positional cloning and sequence analysis of the Drosophila clock gene, timeless. Science 1995;270:805-808.

55.

Bargiello TA , Jackson FR , Young MW Restoration of circadian behavioral rhythms by gene transfer in Drosophila. Nature 1984 ;312:752-754.

56.

Vosshall LB , Pnce JL , Sehgal A. , et al. Block in nuclear localization of penod protein by a second clock mutation timeless. Science 1994;263:1606-1609.

57.

Vitaterna MH , King DP , Chang AM , et al. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 1994,264:719-725.

58.

Ishida N. Molecular biological approach to the circadian clock mechanism. Neurosci Res 1995;23:231-240.

59.

Hall JC Tripping along the trial to the molecular mechanisms of biological clocks . Trends Neurosci 1995;18:230-240.

60.

Amir S. , Stewart J. Resetting of the circadian clock by a conditioned stimulus. Nature 1996;379:542-545

61.

Wray S. , Castel M. , Gamer H. Characterization of the suprachiasmatic nucleus in organotypic slice explant cultures. Microsc Res Tech 1993;25:46-60.

62.

Mirmiran M. , Koster-VanHloffen , Boss , Npa. Circadian rhythm generation in the cultured suprachiasmatic nucleus. Brain Res Bull 1995;38:275-283.