Reciprocal connections between the suprachiasmatic nucleus and the midbrain raphe nuclei: A putative role in the circadian control of behavioral states

  • Samüel Deurveilher
  • Kazue Semba


The primary circadian pacemaker resides within the suprachiasmatic nucleus (SCN) in the hypothalamus, and controls the circadian rhythms of virtually all mammalian behaviors and physiological processes, including sleep and wakefulness. Serotonergic neurons in the midbrain dorsal (DRN) and median (MRN) raphe nuclei have been suggested to play an important role in behavioral state control. These neurons also show circadian rhythmicity in their activity, and may be an important target of the SCN circadian signal for organizing circadian sleep-wake rhythms. There are, however, no direct efferent projections from the SCN to the DRN or the MRN, suggesting that most of the SCN neuronal output may be conveyed indirectly. In this review, we first provide an overview of the anatomical evidence for the indirect neuronal pathways from the SCN to the DRN and MRN via several hypothalamic nuclei, namely, the medial preoptic area, subparaventricular zone, and dorsomedial hypothalamic nucleus. We discuss functional evidence to suggest that the SCN may influence the regulation of sleep-wake states by sending its circadian signal through these indirect pathways to the raphe nuclei. We then consider the feedback projections from the DRN and MRN to the SCN, and discuss functional evidence to suggest that these projections carry feedback information to the SCN regarding the vigilance state of the animal. We hypothesize that the reciprocal interactions between the circadian and sleep-wake regulatory systems may ensure a stable yet adaptive rhythmicity of daily sleepwake cycles.


Circadian Rhythm Raphe Nucleus Dorsal Raphe Nucleus Suprachiasmatic Nucleus Serotonergic Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Moore RY, Leak RH (2001) Suprachiasmatic nucleus in circadian clocks. In: JS Takahashi, FW Turek, RY Moore (eds): Handbook of Behavioral Neurobiology, vol. 12. Kluwer Academic/Plenum Publishers, New York, 141–179Google Scholar
  2. 2.
    Rusak B, Zucker I (1979) Neural regulation of circadian rhythms. Physiol Rev 59: 449–526PubMedGoogle Scholar
  3. 3.
    Guilding C, Piggins HD (2007) Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain? Eur J Neurosci 25: 3195–3216PubMedCrossRefGoogle Scholar
  4. 4.
    Ibuka N, Kawamura H (1975) Loss of circadian rhythm in sleep-wakefulness cycle in the rat by suprachiasmatic nucleus lesions. Brain Res 96: 76–81PubMedCrossRefGoogle Scholar
  5. 5.
    Mouret J, Coindet J, Debilly G, Chouvet G (1978) Suprachiasmatic nuclei lesions in the rat: alterations in sleep circadian rhythms. Electroencephalogr Clin Neurophysiol 45: 402–408PubMedCrossRefGoogle Scholar
  6. 6.
    Mendelson WB, Bergmann BM, Tung A (2003) Baseline and post-deprivation recovery sleep in SCN-lesioned rats. Brain Res 980: 185–190PubMedCrossRefGoogle Scholar
  7. 7.
    Eastman CI, Mistlberger RE, Rechtschaffen A (1984) Suprachiasmatic nuclei lesions eliminate circadian temperature and sleep rhythms in the rat. Physiol Behav 32: 357–368PubMedCrossRefGoogle Scholar
  8. 8.
    Wurts SW, Edgar DM (2000) Circadian and homeostatic control of rapid eye movement (REM) sleep: promotion of REM tendency by the suprachiasmatic nucleus. J Neurosci 20: 4300–4210PubMedGoogle Scholar
  9. 9.
    Edgar D, Dement W, Fuller C (1993) Effect of SCN lesions in squirrel monkeys: evidence for opponent processes in sleep-wake regulation. J Neurosci 13: 1065–1079PubMedGoogle Scholar
  10. 10.
    Easton A, Meerlo P, Bergmann B, Turek FW (2004) The suprachiasmatic nucleus regulates sleep timing and amount in mice. Sleep 27: 1307–1318PubMedGoogle Scholar
  11. 11.
    Mistlberger RE (2005) Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus. Brain Res Rev 49: 429–454PubMedCrossRefGoogle Scholar
  12. 12.
    Pace-Schott EF, Hobson JA (2002) The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 3: 591–605PubMedGoogle Scholar
  13. 13.
    Jones BE (2005) From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci 26: 578–586PubMedCrossRefGoogle Scholar
  14. 14.
    Watts AG (1991) The efferent projections of the suprachiasmatic nucleus: Anatomical insights into the control of circadian rhythms in suprachiasmatic nucleus. In: DC Klein, RY Moore, SM Reppert (eds): The mind’s clock. Oxford University Press, New York, 77–106Google Scholar
  15. 15.
    Card JP (1999) Anatomy of the mammalian circadian timekeeping system. In: R Lydic, HA Baghdoyan (eds): Handbook of behavioral state control: Cellular and molecular mechanisms. CRC Press, Boca Raton, 13–29Google Scholar
  16. 16.
    Morin LP, Allen CN (2006) The circadian visual system, 2005. Brain Res Rev 51: 1–60PubMedCrossRefGoogle Scholar
  17. 17.
    McGinty D, Szymusiak R (2001) Brain structures and mechanisms involved in the generation of NREM sleep: focus on the preoptic hypothalamus. Sleep Med Rev 5: 323–342PubMedCrossRefGoogle Scholar
  18. 18.
    Novak CM, Nunez AA (2000) A sparse projection from the suprachiasmatic nucleus to the sleep active ventrolateral preoptic area in the rat. Neuroreport 11: 93–96PubMedCrossRefGoogle Scholar
  19. 19.
    Chou TC, Bjorkum AA, Gaus SE, Lu J, Scammell TE, Saper CB (2002) Afferents to the ventrolateral preoptic nucleus. J Neurosci 22: 977–990PubMedGoogle Scholar
  20. 20.
    Abrahamson EE, Leak RK, Moore RY (2000) The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 12: 435–440CrossRefGoogle Scholar
  21. 21.
    Hakim H, DeBernardo AP, Silver R (1991) Circadian locomotor rhythms, but not photoperiodic responses, survive surgical isolation of the SCN in hamsters. J Biol Rhythms 6: 97–113PubMedCrossRefGoogle Scholar
  22. 22.
    Silver R, LeSauter J, Tresco PA, Lehman MN (1996) A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature 382: 810–813PubMedCrossRefGoogle Scholar
  23. 23.
    Kramer A, Yang FC, Snodgrass P, Li X, Scammell TE, Davis FC, Weitz CJ (2001) Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Science 294: 2511–2515PubMedCrossRefGoogle Scholar
  24. 24.
    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: 405–410PubMedCrossRefGoogle Scholar
  25. 25.
    Kraves S, Weitz CJ (2006) A role for cardiotrophin-like cytokine in the circadian control of mammalian locomotor activity. Nat Neurosci 9: 212–219PubMedCrossRefGoogle Scholar
  26. 26.
    Meyer-Bernstein EL, Jetton AE, Matsumoto SI, Markuns JF, Lehman MN, Bittman EL (1999) Effects of suprachiasmatic transplants on circadian rhythms of neuroendocrine function in golden hamsters. Endocrinology 140: 207–218PubMedCrossRefGoogle Scholar
  27. 27.
    Jouvet M (1999) Sleep and serotonin: an unfinished story. Neuropsychopharmacology 21: 24S–27SPubMedGoogle Scholar
  28. 28.
    Portas CM, Bjorvatn B, Ursin R (2000) Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies. Prog Neurobiol 60: 13–35PubMedCrossRefGoogle Scholar
  29. 29.
    Ursin R (2002) Serotonin and sleep. Sleep Med Rev 6: 55–69PubMedCrossRefGoogle Scholar
  30. 30.
    Dugovic C (2001) Role of serotonin in sleep mechanisms. Rev Neurol (Paris) 157: S16–19Google Scholar
  31. 31.
    Koella WP, Feldstein A, Czicman JS (1968) The effect of para-chlorophenylalanine on the sleep of cats. Electroencephalogr Clin Neurophysiol 25: 481–490PubMedCrossRefGoogle Scholar
  32. 32.
    Pujol JF, Buguet A, Froment JL, Jones B, Jouvet M (1971) The central metabolism of serotonin in the cat during insomnia. A neurophysiological and biochemical study after administration of p-chlorophenylalanine or destruction of the Raphe system. Brain Res 29: 195–212PubMedCrossRefGoogle Scholar
  33. 33.
    Törk I (1985) Raphe nuclei and serotonin containing systems. In: G Paxinos (ed): The rat nervous system. Academic Press, Sydney, 43–78Google Scholar
  34. 34.
    Jouvet M (1969) Biogenic amines and the states of sleep. Science 163: 32–41PubMedCrossRefGoogle Scholar
  35. 35.
    McGinty DJ, Harper RM (1976) Dorsal raphe neurons: depression of firing during sleep in cats. Brain Res 101: 569–575PubMedCrossRefGoogle Scholar
  36. 36.
    Trulson ME, Jacobs BL (1979) Raphe unit activity in freely moving cats: Correlation with level of behavioral arousal. Brain Res 163: 135–150PubMedCrossRefGoogle Scholar
  37. 37.
    Rasmussen K, Heym J, Jacobs BL (1984) Activity of serotonin-containing neurons in nucleus centralis superior of freely moving cats. Exp Neurol 83: 302–317PubMedGoogle Scholar
  38. 38.
    Trulson ME, Crisp T, Trulson VM (1984) Activity of serotonin-containing nucleus centralis superior (Raphe medianus) neurons in freely moving cats. Exp Brain Res 54: 33–44PubMedCrossRefGoogle Scholar
  39. 39.
    Portas CM, Bjorvatn B, Fagerland S, Grønli J, Mundal V, Sørensen E, Ursin R (1998) On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat. Neuroscience 83: 807–814PubMedCrossRefGoogle Scholar
  40. 40.
    Iwakiri H, Matsuyama K, Mori S (1993) Extracellular levels of serotonin in the medial pontine reticular formation in relation to sleep-wake cycle in cats: a microdialysis study. Neurosci Res 18: 157–170PubMedCrossRefGoogle Scholar
  41. 41.
    Inouye S-IT, Kawamura H (1979) Persistence of circadian rhythmicity in a mammalian hypothalamic “island” containing the suprachiasmatic nucleus. Proc Natl Acad Sci USA 76: 5962–5966PubMedCrossRefGoogle Scholar
  42. 42.
    Janušonis S, Fite KV (2001) Diurnal variation of c-Fos expression in subdivisions of the dorsal raphe nucleus of the Mongolian gerbil (Meriones unguiculatus). J Comp Neurol 440: 31–42PubMedCrossRefGoogle Scholar
  43. 43.
    Birkett M, Fite KV (2005) Diurnal variation in serotonin immunoreactivity in the dorsal raphe nucleus. Brain Res 1034: 180–184PubMedCrossRefGoogle Scholar
  44. 44.
    Kalén P, Rosegren E, Lindvall O, Björklund A (1989) Hippocampal noradrenaline and serotonin release over 24 hours as measured by the dialysis technique in freely moving rats: Correlation to behavioural activity state, effect of handling and tail-pinch. Eur J Neurosci 1: 181–188PubMedCrossRefGoogle Scholar
  45. 45.
    Rueter LE, Jacobs BL (1996) Changes in forebrain serotonin at the light-dark transition: correlation with behaviour. Neuroreport 7: 1107–1111PubMedCrossRefGoogle Scholar
  46. 46.
    Vertes RP, Fortin WJ, Crane AM (1999) Projections of the median raphe nucleus in the rat. J Comp Neurol 407: 555–582PubMedCrossRefGoogle Scholar
  47. 47.
    Vertes RP (1991) A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat. J Comp Neurol 313: 643–668PubMedCrossRefGoogle Scholar
  48. 48.
    Dudley TE, DiNardo LA, Glass JD (1998) Endogenous regulation of serotonin release in the hamster suprachiasmatic nucleus. J Neurosci 18: 5045–5052PubMedGoogle Scholar
  49. 49.
    Barassin S, Raison S, Saboureau M, Bienvenu C, Maîre M, Malan A, Pévet P (2002) Circadian tryptophan hydroxylase levels and serotonin release in the suprachiasmatic nucleus of the rat. Eur J Neurosci 15: 833–840PubMedCrossRefGoogle Scholar
  50. 50.
    Shioiri T, Takahashi K, Yamada N, Takahashi S (1991) Motor activity correlates negatively with free-running period, while positively with serotonin contents in SCN in free-running rats. Physiol Behav 49: 779–786PubMedCrossRefGoogle Scholar
  51. 51.
    Semba J, Toru M, Mataga N (1984) Twenty-four hour rhythms of norepinephrine and serotonin in nucleus suprachiasmaticus, raphe nuclei, and locus coeruleus in the rat. Sleep 7: 211–218PubMedGoogle Scholar
  52. 52.
    Cagampang FRA, Yamazaki S, Otori Y, Inouye S-IT (1993) Serotonin in the raphe nuclei: Regulation by light and an endogenous pacemaker. Neuroreport 5: 49–52PubMedCrossRefGoogle Scholar
  53. 53.
    Ågren H, Koulu M, Saavedra JM, Potter WZ, Linnoila M (1986) Circadian covariation of norepinephrine and serotonin in the locus coeruleus and dorsal raphe nucleus in the rat. Brain Res 397: 353–358PubMedCrossRefGoogle Scholar
  54. 54.
    Ozaki N, Duncan WC Jr, Johnson KA, Wehr TA (1993) Diurnal variations of serotonin and dopamine levels in discrete brain regions of Syrian hamsters and their modification by chronic clorgyline treatment. Brain Res 627: 41–48PubMedCrossRefGoogle Scholar
  55. 55.
    Malek ZS, Pévet P, Raison S (2004) Circadian change in tryptophan hydroxylase protein levels within the rat intergeniculate leaflets and raphe nuclei. Neuroscience 125: 749–758PubMedCrossRefGoogle Scholar
  56. 56.
    Meyer-Bernstein EL, Morin LP (1996) Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. J Neurosci 16: 2097–2111PubMedGoogle Scholar
  57. 57.
    Hay-Schmidt A, Vrang N, Larsen PJ, Mikkelsen JD (2003) Projections from the raphe nuclei to the suprachiasmatic nucleus of the rat. J Chem Neuroanat 25: 293–310PubMedCrossRefGoogle Scholar
  58. 58.
    Moga MM, Moore RY (1997) Organization of neural inputs to the suprachiasmatic nucleus in the rat. J Comp Neurol 389: 508–534PubMedCrossRefGoogle Scholar
  59. 59.
    Malek ZS, Dardente H, Pévet P, Raison S (2005) Tissue-specific expression of tryptophan hydroxylase mRNAs in the rat midbrain: anatomical evidence and daily profiles. Eur J Neurosci 22: 895–901PubMedCrossRefGoogle Scholar
  60. 60.
    Kan JP, Chouvet G, Hery F, Debilly G, Mermet A, Glowinski J, Pujol JF (1977) Daily variations of various parameters of serotonin metabolism in the rat brain. I. Circadian variations of tryptophan-5-hydroxylase in the raphe nuclei and the striatum. Brain Res 123: 125–136PubMedCrossRefGoogle Scholar
  61. 61.
    Malek ZS, Sage D, Pévet P, Raison S (2007) Daily rhythm of tryptophan hydroxylase-2 mRNA within Raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity. Endocrinology doi:10.1210/en.2007-0526Google Scholar
  62. 62.
    Trulson ME, Jacobs BL (1983) Raphe unit activity in freely moving cats: lack of diurnal variation. Neurosci Lett 36: 285–290PubMedCrossRefGoogle Scholar
  63. 63.
    Juvancz P (1980) The effect of raphe lesion on sleep in the rat. Brain Res 194: 371–376PubMedCrossRefGoogle Scholar
  64. 64.
    Mouret J, Coindet J (1980) Polygraphic evidence against a critical role of the raphe nuclei in sleep in the rat. Brain Res 186: 273–287PubMedCrossRefGoogle Scholar
  65. 65.
    Lu J, Sherman D, Devor M, Saper CB (2006) A putative flip-flop switch for control of REM sleep. Nature 441: 589–594PubMedCrossRefGoogle Scholar
  66. 66.
    Mistlberger RE, Antle MC, Glass JD, Miller JD (2000) Behavioral and serotonergic regulation of circadian rhythms. Biol Rhythm Res 31: 240–283CrossRefGoogle Scholar
  67. 67.
    Morin LP (1999) Serotonin and the regulation of mammalian circadian rhythmicity. Ann Med 31: 12–33PubMedGoogle Scholar
  68. 68.
    Deurveilher S, Burns J, Semba K (2002) Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: A dual tract-tracing study in rat. Eur J Neurosci 16: 1195–1213PubMedCrossRefGoogle Scholar
  69. 69.
    Deurveilher S, Semba K (2003) Indirect projections from the suprachiasmatic nucleus to the median preoptic nucleus in rat. Brain Res 987: 100–106PubMedCrossRefGoogle Scholar
  70. 70.
    Deurveilher S, Semba K (2005) Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state. Neuroscience 130: 165–183PubMedCrossRefGoogle Scholar
  71. 71.
    Leak RK, Moore RY (2001) Topographic organization of suprachiasmatic nucleus projection neurons. J Comp Neurol 433: 312–334PubMedCrossRefGoogle Scholar
  72. 72.
    Watts AG, Swanson LW (1987) Efferent projections of the suprachiasmatic nucleus: II. Studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat. J Comp Neurol 258: 230–252PubMedCrossRefGoogle Scholar
  73. 73.
    Thompson RH, Canteras NS, Swanson LW (1996) Organization of projections from the dorsomedial nucleus of the hypothalamus: A PHA-L study in the rat. J Comp Neurol 376: 143–173PubMedCrossRefGoogle Scholar
  74. 74.
    Leak RK, Card JP, Moore RY (1999) Suprachiasmatic pacemaker organization analyzed by viral transynaptic transport. Brain Res 819: 23–32PubMedCrossRefGoogle Scholar
  75. 75.
    Thompson RH, Swanson LW (1998) Organization of inputs to the dorsomedial nucleus of the hypothalamus: a reexamination with Fluorogold and PHA-L in the rat. Brain Res Rev 27: 89–118PubMedCrossRefGoogle Scholar
  76. 76.
    Kriegsfeld LJ, Leak RK, Yackulic CB, LeSauter J, Silver R (2004) Organization of suprachiasmatic nucleus projections in Syrian hamsters (Mesocricetus auratus): an anterograde and retrograde analysis. J Comp Neurol 468: 361–379PubMedCrossRefGoogle Scholar
  77. 77.
    Buijs RM, Markman M, Nunes-Cardoso B, Hou Y-X, Shinn S (1993) Projections of the suprachiasmatic nucleus to stress-related areas in the rat hypothalamus: A light and electron microscopic study. J Comp Neurol 335: 42–54PubMedCrossRefGoogle Scholar
  78. 78.
    Watts AG, Swanson LW, Sanchez-Watts G (1987) Efferent projections of the suprachiasmatic nucleus: I. Studies using anterograde transport of Phaseolus vulgaris leucoagglutinin in the rat. J Comp Neurol 258: 204–229PubMedCrossRefGoogle Scholar
  79. 79.
    Berk M, Finkelstein J (1981) An autoradiographic determination of the efferent projections of the suprachiasmatic nucleus of the hypothalamus. Brain Res 226: 1–13PubMedCrossRefGoogle Scholar
  80. 80.
    Stephan FK, Berkley KJ, Moss RL (1981) Efferent connections of the rat suprachiasmatic nucleus. Neuroscience 6: 2625–2641PubMedCrossRefGoogle Scholar
  81. 81.
    Kalsbeek A, Teclemariam-Mesbah R, Pévet P (1993) Efferent projections of the suprachiasmatic nucleus in the golden hamster (Mesocricetus auratus). J Comp Neurol 332: 293–314PubMedCrossRefGoogle Scholar
  82. 82.
    Hoorneman EMD, Buijs RM (1982) Vasopressin fiber pathways in the rat brain following suprachiasmatic nucleus lesioning. Brain Res 243: 235–241PubMedCrossRefGoogle Scholar
  83. 83.
    van der Beek EM, Wiegant VM, van der Donk HA, van der Hurk R, Buijs RM (1993) Lesions of the suprachiasmatic nucleus indicate the presence of a direct vasoactive intestinal polypeptide-containing projection to gonadotophin-releasing hormone neurons in the female rat. J Neuroendocrinol 5: 137–144PubMedCrossRefGoogle Scholar
  84. 84.
    Abrahamson EE, Moore RY (2001) Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res 916: 172–191PubMedCrossRefGoogle Scholar
  85. 85.
    van den Pol AN, Tsujimoto KL (1985) Neurotransmitters of the hypothalamic suprachiasmatic nucleus: immunocytochemical analysis of 25 neuronal antigens. Neuroscience 15: 1049–1086PubMedCrossRefGoogle Scholar
  86. 86.
    Vrang N, Larsen PJ, Moller M, Mikkelsen JD (1995) Topographical organization of the rat suprachiasmatic-paraventricular projection. J Comp Neurol 353: 585–603PubMedCrossRefGoogle Scholar
  87. 87.
    Moore RY, Speh JC (1993) GABA is the principal neurotransmitter of the circadian system. Neurosci Lett 150: 112–116PubMedCrossRefGoogle Scholar
  88. 88.
    Morin LP, Blanchard JH (2001) Neuromodulator content of hamster intergeniculate leaflet neurons and their projection to the suprachiasmatic nucleus or visual midbrain. J Comp Neurol 437: 79–90PubMedCrossRefGoogle Scholar
  89. 89.
    Buijs RM, Hou Y-X, Shinn S, Renaud LP (1994) Ultrastructural evidence for intraand extranuclear projections of GABAergic neurons of the suprachiasmatic nucleus. J Comp Neurol 340: 381–391PubMedCrossRefGoogle Scholar
  90. 90.
    Hermes ML, Coderre EM, Buijs RM, Renaud LP (1996) GABA and glutamate mediate rapid neurotransmission from suprachiasmatic nucleus to hypothalamic paraventricular nucleus in rat. J Physiol 496: 749–757PubMedGoogle Scholar
  91. 91.
    Sun X, Whitefield S, Rusak B, Semba K (2001) Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in rat: implications for circadian control of behavioral state. Eur J Neurosci 14: 1257–1274PubMedCrossRefGoogle Scholar
  92. 92.
    Saint-Mleux B, Bayer L, Eggermann E, Jones BE, Mühlethaler M, Serafin M (2007) Suprachiasmatic modulation of noradrenaline release in the ventrolateral preoptic nucleus. J Neurosci 27: 6412–6416PubMedCrossRefGoogle Scholar
  93. 93.
    Buijs RM, Wortel J, Hou YX (1995) Colocalization of gamma-aminobutyric acid with vasopressin, vasoactive intestinal peptide, and somatostatin in the rat suprachiasmatic nucleus. J Comp Neurol 358: 343–352PubMedCrossRefGoogle Scholar
  94. 94.
    ter Horst GJ, Luiten PG (1986) The projections of the dorsomedial hypothalamic nucleus in the rat. Brain Res Bull 16: 231–248PubMedCrossRefGoogle Scholar
  95. 95.
    Swanson LW, Mogenson GJ, Simerly RB, Wu M (1987) Anatomical and electrophysiological evidence for a projection from the medial preoptic area to the “mesencephalic and subthalamic locomotor regions” in the rat. Brain Res 405: 108–122PubMedCrossRefGoogle Scholar
  96. 96.
    Simerly RB, Swanson LW (1988) Projections of the medial preoptic nucleus: a phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J Comp Neurol 270: 209–242PubMedCrossRefGoogle Scholar
  97. 97.
    Steininger TL, Gong H, McGinty D, Szymusiak R (2001) Subregional organization of preoptic area/anterior hypothalamic projections to arousal-related monoaminergic cell groups. J Comp Neurol 429: 638–653PubMedCrossRefGoogle Scholar
  98. 98.
    Chiba T, Murata Y (1985) Afferent and efferent connections of the medial preoptic area in the rat: a WGA-HRP study. Brain Res Bull 14: 261–272PubMedCrossRefGoogle Scholar
  99. 99.
    Kalén P, Karlson M, Wiklund L (1985) Possible excitatory amino acid afferents to nucleus raphe dorsalis of the rat investigated with retrograde wheat germ agglutinin and d-3H]aspartate tracing. Brain Res 360: 285–297PubMedCrossRefGoogle Scholar
  100. 100.
    Peschanski M, Besson J-M (1984) Diencephalic connections of the raphe nuclei of the rat brainstem: An anatomical study with reference to the somatosensory system. J Comp Neurol 224: 509–534PubMedCrossRefGoogle Scholar
  101. 101.
    Aghajanian GK, Wang RY (1977) Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique. Brain Res 122: 229–242PubMedCrossRefGoogle Scholar
  102. 102.
    Semba K, Reiner PB, McGeer EG, Fibiger HC (1989) Brainstem projecting neurons in the rat basal forebrain: neurochemical, topographical, and physiological distinctions from cortically projecting cholinergic neurons. Brain Res Bull 22: 501–509PubMedCrossRefGoogle Scholar
  103. 103.
    Peyron C, Petit J-M, Rampon C, Jouvet M, Luppi P-H (1998) Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods. Neuroscience 82: 443–468PubMedCrossRefGoogle Scholar
  104. 104.
    Lee HS, Park SH, Song WC, Waterhouse BD (2005) Retrograde study of hypocretin-1 (orexin-A) projections to subdivisions of the dorsal raphe nucleus in the rat. Brain Res 1059: 35–45PubMedCrossRefGoogle Scholar
  105. 105.
    Gervasoni D, Peyron C, Rampon C, Barbagli B, Chouvet G, Urbain N, Fort P, Luppi P-H (2000) Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons. J Neurosci 20: 4217–4225PubMedGoogle Scholar
  106. 106.
    Simerly RB, Gorski RA, Swanson LW (1986) Neurotransmitter specificity of cells and fibers in the medial preoptic nucleus: an immunohistochemical study in the rat. J Comp Neurol 246: 343–363PubMedCrossRefGoogle Scholar
  107. 107.
    Skofitsch G, Jacobowitz DM (1985) Immunohistochemical mapping of galanin-like neurons in the rat central nervous system. Peptides 6: 509–546PubMedCrossRefGoogle Scholar
  108. 108.
    Moga MM, Saper CB (1994) Neuropeptide-immunoreactive neurons projecting to the paraventricular hypothalamic nucleus in the rat. J Comp Neurol 346: 137–150PubMedCrossRefGoogle Scholar
  109. 109.
    Chou TC, Scammell TE, Gooley JJ, Gaus SE, Saper C, Lu J (2003) Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms. J Neurosci 23: 10691–10702PubMedGoogle Scholar
  110. 110.
    Valentino RJ, Commons KG (2005) Peptides that fine-tune the serotonin system. Neuropeptides 39: 1–8PubMedCrossRefGoogle Scholar
  111. 111.
    Xu ZQ, Zhang X, Pieribone VA, Grillner S, Hökfelt T (1998) Galanin-5-hydroxytryptamine interactions: Electrophysiological, immunohistochemical and in situ hybridization studies on rat dorsal raphe neurons with a note on galanin R1 and R2 receptors. Neuroscience 87: 79–94PubMedCrossRefGoogle Scholar
  112. 112.
    Brown RE, Sergeeva OA, Eriksson KS, Haas HL (2002) Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline). J Neurosci 22: 8850–8859PubMedGoogle Scholar
  113. 113.
    Nanopoulos D, Belin MF, Maître M, Vincendon G, Pujol JF (1982) Immunocytochemical evidence for the existence of GABAergic neurons in the nucleus raphe dorsalis. Possible existence of neurons containing serotonin and GABA. Brain Res 232: 375–389PubMedCrossRefGoogle Scholar
  114. 114.
    Trulson ME, Cannon MS, Raese JD (1985) Identification of dopamine-containing cell bodies in the dorsal and median raphe nuclei of the rat brain using tyrosine hydroxylase immunochemistry. Brain Res Bull 15: 229–234PubMedCrossRefGoogle Scholar
  115. 115.
    Clements JR, Madl JE, Johnson RL, Larson AA, Beitz AJ (1987) Localization of glutamate, glutaminase, aspartate and aspartate aminotransferase in the rat midbrain periaqueductal gray. Exp Brain Res 67: 594–602PubMedCrossRefGoogle Scholar
  116. 116.
    Terkel J, Johnson JH, Whitmoyer DI, Sawyer CH (1974) Effect of adrenalectomy on a diurnal (circadian) rhythm in hypothalamic multiple unit activitiy in the female rat. Neuroendocrinology 14: 103–113PubMedGoogle Scholar
  117. 117.
    Inouye S-IT (1983) Does the ventromedial hypothalamic nucleus contain a self-sustained circadian oscillator associated with periodic feedings? Brain Res 279: 53–63PubMedCrossRefGoogle Scholar
  118. 118.
    Yamazaki S, Kerbeshian MC, Hocker CG, Block GD, Menaker M (1998) Rhythmic properties of the hamster suprachiasmatic nucleus in vivo J Neurosci 18: 10709–10723PubMedGoogle Scholar
  119. 119.
    Choi S, Wong LS, Yamat C, Dallman MF (1998) Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator? J Neurosci 18: 3843–3852PubMedGoogle Scholar
  120. 120.
    Gooley JJ, Schomer A, Saper CB (2006) The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms. Nat Neurosci 9: 398–407PubMedCrossRefGoogle Scholar
  121. 121.
    Lee Y, Arbogast LA, Voogt JL (1998) Semicircadian rhythms of c-Fos expression in several hypothalamic areas during pregnancy in the rat: relationship to prolactin secretion. Neuroendocrinology 67: 83–93PubMedCrossRefGoogle Scholar
  122. 122.
    Nunez AA, Bult A, McElhinny TL, Smale L (1999) Daily rhythms of Fos expression in hypothalamic targets of the suprachiasmatic nucleus in diurnal and nocturnal rodents. J Biol Rhythms 14: 300–306PubMedCrossRefGoogle Scholar
  123. 123.
    Schwartz MD, Nunez AA, Smale L (2004) Differences in the suprachiasmatic nucleus and lower subparaventricular zone of diurnal and nocturnal rodents. Neuroscience 127: 13–23PubMedCrossRefGoogle Scholar
  124. 124.
    Smale L, Castleberry C, Nunez AA (2001) Fos rhythms in the hypothalamus of Rattus and Arvicanthis that exhibit nocturnal and diurnal patterns of rhythmicity. Brain Res 899: 101–105PubMedCrossRefGoogle Scholar
  125. 125.
    Schwartz MD, Smale L (2005) Individual differences in rhythms of behavioral sleep and its neural substrates in Nile grass rats. J Biol Rhythms 20: 526–537PubMedCrossRefGoogle Scholar
  126. 126.
    Asala SA, Okano Y, Honda K, Inoue S (1990) Effects of medial preoptic area lesions on sleep and wakefulness in unrestrained rats. Neurosci Lett 114: 300–304PubMedCrossRefGoogle Scholar
  127. 127.
    Lu J, Greco MA, Shiromani P, Saper CB (2000) Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep. J Neurosci 20: 3830–3842PubMedGoogle Scholar
  128. 128.
    John J, Kumar VM (1998) Effect of NMDA lesion of the medial preoptic neurons on sleep and other functions. Sleep 21: 587–598PubMedGoogle Scholar
  129. 129.
    Srividya R, Mallick HN, Kumar VM (2006) Differences in the effects of medial and lateral preoptic lesions on thermoregulation and sleep in rats. Neuroscience 139: 853–864PubMedCrossRefGoogle Scholar
  130. 130.
    Lu J, Zhang Y-H, Chou T, Gaus SE, Elmquist JK, Shiromani P, Saper CB (2001) Contrasting effects of ibotenate lesions of the paraventricular nucleus and subparaventricular zone on sleep-wake cycle and temperature regulation. J Neurosci 21: 4864–4874PubMedGoogle Scholar
  131. 131.
    Abrahamson EE, Moore RY (2006) Lesions of suprachiasmatic nucleus efferents selectively affect rest-activity rhythm. Mol Cell Endocrinol 252: 46–56PubMedCrossRefGoogle Scholar
  132. 132.
    Moore RY, Danchenko RL (2002) Paraventricular-subparaventricular hypothalamic lesions selectively affect circadian function. Chronobiol Int 19: 345–360PubMedCrossRefGoogle Scholar
  133. 133.
    Landry GJ, Simon MM, Webb IC, Mistlberger RE (2006) Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats. Am J Physiol Regul Integr Comp Physiol 290: R1527–R1534PubMedGoogle Scholar
  134. 134.
    Bellinger LL, Bernardis LL, Mendel VE (1976) Effect of ventromedial and dorsomedial hypothalamic lesions on circadian corticosterone rhythms. Neuroendocrinology 22: 216–225PubMedGoogle Scholar
  135. 135.
    Mistlberger RE (1994) Circadian food-anticipatory activity: formal models and physiological mechanisms. Neurosci Biobehav Rev 18: 171–195PubMedCrossRefGoogle Scholar
  136. 136.
    Buijs RM, la Fleur SE, Wortel J, Van Heyningen C, Zuiddam L, Mettenleiter TC, Kalsbeek A, Nagai K, Niijima A (2003) The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. J Comp Neurol 464: 36–48PubMedCrossRefGoogle Scholar
  137. 137.
    Alam MN, McGinty D, Szymusiak R (1995) Neuronal discharge of preoptic/anterior hypothalamic thermosensitive neurons: relation to NREM sleep. Am J Physiol 269: R1240–R1249PubMedGoogle Scholar
  138. 138.
    Methippara MM, Alam MN, Szymusiak R, McGinty D (2003) Preoptic area warming inhibits wake-active neurons in the perifornical lateral hypothalamus. Brain Res 960: 165–173PubMedCrossRefGoogle Scholar
  139. 139.
    Alam MN, McGinty D, Szymusiak R (1995) Preoptic/anterior hypothalamic neurons: thermosensitivity in rapid eye movement sleep. Am J Physiol 269: R1250–R1257PubMedGoogle Scholar
  140. 140.
    Guzman-Marin R, Alam MN, Szymusiak R, Drucker-Colin R, Gong H, McGinty D (2000) Discharge modulation of rat dorsal raphe neurons during sleep and waking: effects of preoptic/basal forebrain warming. Brain Res 875: 23–34PubMedCrossRefGoogle Scholar
  141. 141.
    Zaretskaia MV, Zaretsky DV, Shekhar A, DiMicco JA (2002) Chemical stimulation of the dorsomedial hypothalamus evokes non-shivering thermogenesis in anesthetized rats. Brain Res 928: 113–125PubMedCrossRefGoogle Scholar
  142. 142.
    Saper CB, Lu J, Chou TC, Gooley J (2005) The hypothalamic integrator for circadian rhythms. Trends Neurosci 28: 152–157PubMedCrossRefGoogle Scholar
  143. 143.
    Tischler RC, Morin LP (2003) Reciprocal serotonergic connections between the hamster median and dorsal raphe nuclei. Brain Res 981: 126–132PubMedCrossRefGoogle Scholar
  144. 144.
    Mrosovsky N (1996) Locomotor activity and non-photic influences on circadian clocks. Biol Rev Camb Philos Soc 71: 343–372PubMedCrossRefGoogle Scholar
  145. 145.
    Reebs SG, Mrosovsky N (1989) Effects of induced wheel running on the circadian activity rhythms of Syrian hamsters: entrainment and phase response curve. J Biol Rhythms 4: 39–48PubMedCrossRefGoogle Scholar
  146. 146.
    Antle MC, Mistlberger RE (2000) Circadian clock resetting by sleep deprivation without exercise in the Syrian hamster. J Neurosci 20: 9326–9332PubMedGoogle Scholar
  147. 147.
    Mistlberger RE, Antle MC, Webb IC, Jones M, Weinberg J, Pollock MS (2003) Circadian clock resetting by arousal in Syrian hamsters: the role of stress and activity. Am J Physiol Regul Integr Comp Physiol 285: R917–R925PubMedGoogle Scholar
  148. 148.
    Medanic M, Gillette MU (1992) Serotonin regulates the phase of the rat suprachiasmatic circadian pacemaker in vitro only during the subjective day. J Physiol 450: 629–642PubMedGoogle Scholar
  149. 149.
    Ehlen JC, Grossman GH, Glass JD (2001) In vivo resetting of the hamster circadian clock by 5-HT7 receptors in the suprachiasmatic nucleus. J Neurosci 21: 5351–5357PubMedGoogle Scholar
  150. 150.
    Glass JD, DiNardo LA, Ehlen JC (2000) Dorsal raphe nuclear stimulation of SCN serotonin release and circadian phase-resetting. Brain Res 859: 224–232PubMedCrossRefGoogle Scholar
  151. 151.
    Meyer-Bernstein EL, Morin LP (1999) Electrical stimulation of the median or dorsal raphe nuclei reduces light-induced FOS protein in the suprachiasmatic nucleus and causes circadian activity rhythm phase shifts. Neuroscience 92: 267–279PubMedCrossRefGoogle Scholar
  152. 152.
    Dudley TE, Dinardo LA, Glass JD (1999) In vivo assessment of the midbrain raphe nuclear regulation of serotonin release in the hamster suprachiasmatic nucleus. J Neurophysiol 81: 1469–1477PubMedGoogle Scholar
  153. 153.
    Grossman GH, Mistlberger RE, Antle MC, Ehlen JC, Glass JD (2000) Sleep deprivation stimulates serotonin release in the suprachiasmatic nucleus. Neuroreport 11: 1929–1932PubMedCrossRefGoogle Scholar
  154. 154.
    Edgar DM, Reid MS, Dement WC (1997) Serotonergic afferents mediate activity-dependent entrainment of the mouse circadian clock. Am J Physiol 273: R265–R269PubMedGoogle Scholar
  155. 155.
    Marchant EG, Watson NV, Mistlberger RE (1997) Both neuropeptide Y and serotonin are necessary for entrainment of circadian rhythms in mice by daily treadmill running schedules. J Neurosci 17: 7974–7987PubMedGoogle Scholar
  156. 156.
    Bobrzynska KJ, Vrang N, Mrosovsky N (1996) Persistence of nonphotic phase shifts in hamsters after serotonin depletion in the suprachiasmatic nucleus. Brain Res 741: 205–214PubMedCrossRefGoogle Scholar
  157. 157.
    Antle MC, Marchant EG, Niel L, Mistlberger RE (1998) Serotonin antagonists do not attenuate activity-induced phase shifts of circadian rhythms in the Syrian hamster. Brain Res 813: 139–149PubMedCrossRefGoogle Scholar
  158. 158.
    Biello SM, Janik D, Mrosovsky N (1994) Neuropeptide Y and behaviorally induced phase shifts. Neuroscience 62: 273–279PubMedCrossRefGoogle Scholar
  159. 159.
    Glotzbach S, Cornett C, Heller H (1987) Activity of suprachiasmatic and hypothalamic neurons during sleep and wakefulness in the rat. Brain Res 419: 279–287PubMedCrossRefGoogle Scholar
  160. 160.
    Deboer T, Vansteensel MJ, Détári L, Meijer JH (2003) Sleep states alter activity of suprachiasmatic nucleus neurons. Nat Neurosci 6: 1086–1090PubMedCrossRefGoogle Scholar
  161. 161.
    Mason R (1986) Circadian variation in sensitivity of suprachiasmatic and lateral geniculate neurones to 5-hydroxytryptamine in the rat. J Physiol 377: 1–13PubMedGoogle Scholar
  162. 162.
    Ying S-W, Rusak B (1994) Effects of serotonergic agonists on firing rates of photically responsive cells in the hamster suprachiasmatic nucleus. Brain Res 651: 37–46PubMedCrossRefGoogle Scholar
  163. 163.
    Deboer T, Détári L, Meijer JH (2007) Long term effects of sleep deprivation on the mammalian circadian pacemaker. Sleep 30: 257–262PubMedGoogle Scholar
  164. 164.
    Morin LP, Shivers KY, Blanchard JH, Muscat L (2006) Complex organization of mouse and rat suprachiasmatic nucleus. Neuroscience 137: 1285–1297PubMedCrossRefGoogle Scholar
  165. 165.
    Glass JD, Selim M, Rea MA (1994) Modulation of light-induced c-Fos expression in the suprachiasmatic nuclei by 5-HT1A receptor agonists. Brain Res 638: 235–242PubMedCrossRefGoogle Scholar
  166. 166.
    Rea MA, Glass JD, Colwell CS (1994) Serotonin modulates photic responses in the hamster suprachiasmatic nuclei. J Neurosci 14: 3635–3642PubMedGoogle Scholar
  167. 167.
    Pickard GE, Weber ET, Scott PA, Riberdy AF, Rea MA (1996) 5HT1B receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c-fos in the suprachiasmatic nucleus. J Neurosci 16: 8208–8220PubMedGoogle Scholar
  168. 168.
    Pickard GE, Smith BN, Belenky M, Rea MA, Dudek FE, Sollars PJ (1999) 5-HT1B receptor-mediated presynaptic inhibition of retinal input to the suprachiasmatic nucleus. J Neurosci 19: 4034–4045PubMedGoogle Scholar
  169. 169.
    Aston-Jones G, Chen S, Zhu Y, Oshinsky ML (2001) A neural circuit for circadian regulation of arousal. Nature 4: 732–738Google Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2008

Authors and Affiliations

  • Samüel Deurveilher
    • 1
  • Kazue Semba
    • 1
  1. 1.Department of Anatomy and Neurobiology, Faculty of MedicineDalhousie UniversityHalifaxCanada

Personalised recommendations