Efferent and afferent connections of the dorsal and median raphe nuclei in the rat

  • Robert P. Vertes
  • Stephanie B. Linley


It is well established that the brainstem contains discrete groups of serotonin-containing neurons with extensive axonal processes that distribute throughout the neuroaxis. Serotonergic neurons have been implicated in a range of functions prominently including the modulation of various events and states of sleep. We describe the efferent and afferent projections of the dorsal raphe (DR) and the median raphe (MR) nuclei. DR fibers distribute widely throughout the forebrain to dopamine-containing nuclei of the ventral midbrain, the lateral hypothalamus, the midline thalamus, amygdala, the dorsal and ventral striatum and adjoining regions of the basal forebrain, and most of the cortex. In contrast to the DR, the MR is a midline/paramidline system of projections. Specifically, MR fibers mainly distribute to forebrain structures lying on or close to the midline including the medial mammillary and supramammillary nuclei, posterior and perifornical nuclei of hypothalamus, midline and intralaminar nuclei of thalamus, lateral habenula, medial zona incerta, diagonal band nuclei, septum and hippocampus. Overall, MR projections to the cortex are light. With few exceptions, DR and MR project to separate, non-overlapping regions of the forebrain — or, in effect, DR and MR share the serotonergic innervation of the forebrain. Although their outputs are distinct, DR and MR receive common sets of afferent projections from “limbic” cortices, the medial and lateral preoptic areas, lateral habenula, the perifornical, lateral and dorsomedial nuclei of hypothalamus, and several brainstem nuclei prominently including the midbrain and pontine central gray, locus coeruleus, laterodorsal tegmental nucleus and caudal raphe groups. In addition to common afferents, DR receives significant projections from bed nucleus of stria terminalis, lateral septum, diagonal band nuclei, substantia nigra and the tuberomammillary nucleus, while MR receives distinct projections from the medial septum, mammillary nuclei and the interpeduncular nucleus. There are few projections from the amygdala to either DR or MR. In effect, the DR and MR are positioned to integrate of vast array of information from the brainstem and limbic forebrain and through their extensive axonal network influence virtually all parts of the neuro


Ventral Tegmental Area Basal Forebrain Raphe Nucleus Dorsal Raphe Dorsal Raphe Nucleus 
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  1. 1.
    Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72: 165–229PubMedGoogle Scholar
  2. 2.
    Datta S, Maclean RR (2007) Neurobiological mechanisms for the regulation of mammalian sleep-wake behavior: Reinterpretation of historical evidence and inclusion of contemporary cellular and molecular evidence. Neurosci Biobehav Rev 31: 775–824PubMedCrossRefGoogle Scholar
  3. 3.
    Dalhstrom A, Fuxe K (1964) Evidence for the existence of monoamine containing neurons in the central nervous system: I. Demonstrations of monoamines in cell bodies of brainstem neurons. Acta Physiol Scand 232: 1–55Google Scholar
  4. 4.
    Halliday G, Harding A, Paxinos G (1995) Serotonin and tachykinin systems. In: G Paxinos (ed): The rat nervous system. Academic Press, New York, 929–974Google Scholar
  5. 5.
    Harding A, Paxinos G, Halliday G (2004) The serotonin and tachykinin systems. In: G Paxinos (ed): The rat nervous system. Elsevier Academic Press, New York, 1205–1256Google Scholar
  6. 6.
    Arita H, Sakamoto M, Hirokawa Y, Okado N (1993) Serotonin innervation patterns differ among the various medullary motoneuronal groups involved in upper airway control. Exp Brain Res 95: 100–110PubMedCrossRefGoogle Scholar
  7. 7.
    Vertes RP, Crane AM (1997) Distribution, quantification, and morphological characteristics of serotonin-immunoreactive cells of the supralemniscal nucleus (B9) and pontomesencephalic reticular formation in the rat. J Comp Neurol 378: 411–424PubMedCrossRefGoogle Scholar
  8. 8.
    Vertes RP, Martin GF (1988) Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat. J Comp Neurol 275: 511–541PubMedCrossRefGoogle Scholar
  9. 9.
    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
  10. 10.
    Morin, LP, Meyer-Bernstein EL (1999) The ascending serotonergic system in the hamster: comparison with projections of the dorsal and median raphe nuclei. Neuroscience 91: 81–105PubMedCrossRefGoogle Scholar
  11. 11.
    Vertes RP, Fortin WJ, Crane AM (1999) Projections of the median raphe nucleus in the rat. J Comp Neurol 407: 555–582PubMedCrossRefGoogle Scholar
  12. 12.
    Aznar S, Qian ZX, Knudsen GM (2004) Non-serotonergic dorsal and median raphe projection onto parvalbumin-and calbindin-containing neurons in hippocampus and septum. Neuroscience 124: 573–581PubMedCrossRefGoogle Scholar
  13. 13.
    Kapur S, Remington G (1996) Serotonin-dopamine interaction and its relevance to schizophrenia. Am J Psychiatry 153: 466–476PubMedGoogle Scholar
  14. 14.
    Descarries L, Watkins KC, Garcia S, Beaudet A (1982) The serotonin neurons in nucleus raphe dorsalis of adult rat: a light and electron microscopic radioautographic study. J Comp Neurol 207: 239–254PubMedCrossRefGoogle Scholar
  15. 15.
    Moore RY, Halaris AE, Jones BE (1978) Serotonin neurons of the midbrain raphe: ascending projections. J Comp Neurol 180: 417–438PubMedCrossRefGoogle Scholar
  16. 16.
    Azmitia EC, Segal M (1978) An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat. J Comp Neurol 179: 641–667PubMedCrossRefGoogle Scholar
  17. 17.
    Vertes RP, Kocsis B (1994) Projections of the dorsal raphe nucleus to the brainstem: PHA-L analysis in the rat. J Comp Neurol 340: 11–26PubMedCrossRefGoogle Scholar
  18. 18.
    Vertes RP (1988) Brainstem afferents to the basal forebrain in the rat. Neuroscience 24: 907–935PubMedCrossRefGoogle Scholar
  19. 19.
    Di Matteo V, Cacchio M, Di Giulio C, Esposito E (2002) Role of serotonin (2C) receptors in the control of brain dopaminergic function. Pharmacol Biochem Behav 71: 727–734PubMedCrossRefGoogle Scholar
  20. 20.
    Krout KE, Belzer RE, Loewy AD (2002) Brainstem projections to midline and intralaminar thalamic nuclei of the rat. J Comp Neurol 448: 53–101PubMedCrossRefGoogle Scholar
  21. 21.
    McKenna JT, Vertes RP (2004) Afferent projections to nucleus reuniens of the thalamus. J Comp Neurol 480: 115–142PubMedCrossRefGoogle Scholar
  22. 22.
    Pechanski M, Besson JM (1984) Diencephalic connections of the raphe nuclei of the rat brainstem: an anatomical study with reference to the somatosensory system. J Comp Neurol 224: 509–534CrossRefGoogle Scholar
  23. 23.
    Villar MJ, Vitale ML, Hokfelt T, Verhofstad AA (1988) Dorsal raphe serotoninergic branching neurons projecting both to the lateral geniculate body and superior colliculus: a combined retrograde tracing-immunohistochemical study in the rat. J Comp Neurol 277: 126–140PubMedCrossRefGoogle Scholar
  24. 24.
    Van der Werf YD, Witter MP, Groenewegen HJ (2002) The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res Rev 39: 107–140PubMedCrossRefGoogle Scholar
  25. 25.
    Vertes RP, Hoover WB, Do Valle AC, Sherman A, Rodriguez JJ (2006) Efferent projections of reuniens and rhomboid nuclei of the thalamus in the rat. J Comp Neurol 499: 768–796PubMedCrossRefGoogle Scholar
  26. 26.
    Vertes RP, Hoover WB, Szigeti-Buck K, Leranth C (2007) Nucleus reuniens of the midline thalamus: Link between the medial prefrontal cortex and the hippocampus. Brain Res Bull 71: 601–609PubMedCrossRefGoogle Scholar
  27. 27.
    Bentivoglio M, Balercia G, Kruger L (1991). The specificity of the nonspecific thalamus: the midline nuclei. Prog Brain Res 87: 53–80PubMedCrossRefGoogle Scholar
  28. 28.
    Vertes RP (2006) Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142: 1–20PubMedCrossRefGoogle Scholar
  29. 29.
    Herkenham M (1978) The connections of the nucleus reuniens thalami: evidence for a direct thalamo-hippocampal pathway in the rat. J Comp Neurol 177: 589–610PubMedCrossRefGoogle Scholar
  30. 30.
    Risold PY, Thompson RH, Swanson LW (1997) The structural organization of connections between hypothalamus and cerebral cortex. Brain Res Rev 24: 197–254PubMedCrossRefGoogle Scholar
  31. 31.
    Vertes RP (2002) Analysis of projections from the medial prefrontal cortex to the thalamus in the rat, with emphasis on nucleus reuniens. J Comp Neurol 442: 163–187PubMedCrossRefGoogle Scholar
  32. 32.
    Viana Di Prisco G, Vertes RP (2006) Excitatory actions of the ventral midline thalamus (rhomboid/reuniens) on the medial prefrontal cortex in the rat. Synapse 60: 45–55CrossRefGoogle Scholar
  33. 33.
    Bayer L, Eggermann E, Saint-Mleux B, Machard D, Jones BE, Muhlethaler M, Serafin M (2002) Selective action of orexin (hypocretin) on nonspecific thalamocortical projection neurons. J Neurosci 22: 7835–7839PubMedGoogle Scholar
  34. 34.
    Huang H, Ghosh P, van den Pol AN (2006) Prefrontal cortex-projecting glutamatergic thalamic paraventricularnucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal. J Neurophysiol 95: 1656–1668PubMedCrossRefGoogle Scholar
  35. 35.
    Gasbarri A, Sulli A, Pacitti C, McGaugh JL (1999) Serotonergic input to cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis in the rat. Neuroscience 91: 1129–1142PubMedCrossRefGoogle Scholar
  36. 36.
    Zaborszky L (2002) The modular organization of brain systems. Basal forebrain: the last frontier. Prog Brain Res 136: 359–372PubMedGoogle Scholar
  37. 37.
    Rye DB, Wainer BH, Mesulam MM, Mufson EJ, Saper CB (1984) Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neuroscience 13: 627–643PubMedCrossRefGoogle Scholar
  38. 38.
    Woolf NJ, Eckenstein F, Butcher LL (1984) Cholinergic systems in the rat brain: I. Projections to the limbic telencephalon. Brain Res Bull 13: 751–784PubMedCrossRefGoogle Scholar
  39. 39.
    Luiten PG, Gaykema RP, Traber J, Spencer DG Jr (1987) Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transported Phaseolus vulgaris leucoagglutinin. Brain Res 413: 229–250PubMedCrossRefGoogle Scholar
  40. 40.
    Woolf NJ (1991) Cholinergic systems in mammalian brain and spinal cord. Prog Neurobiol 37: 475–524PubMedCrossRefGoogle Scholar
  41. 41.
    Jones BE (2004) Activity, modulation and role of basal forebrain cholinergic neurons innervating the cerebral cortex. Prog Brain Res 145: 157–169PubMedGoogle Scholar
  42. 42.
    Sarter M, Hasselmo ME, Bruno JP, Givens B (2005) Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Res Rev 48: 98–111PubMedCrossRefGoogle Scholar
  43. 43.
    Hensler JG (2006) Serotonergic modulation of the limbic system. Neurosci Biobehav Rev 30: 203–214PubMedCrossRefGoogle Scholar
  44. 44.
    Steriade M, McCarley RW (1990) Brainstem control of wakefulness and sleep. Plenum Press, New YorkGoogle Scholar
  45. 45.
    Vertes RP (1990) Brainstem mechanisms of slow-wave sleep and REM sleep. In: WR Klemm, RP Vertes (eds): Brainstem mechanisms of behavior. John Wiley & Sons, New York, 535–583Google Scholar
  46. 46.
    Jones BE (2005) From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci 26: 578–586PubMedCrossRefGoogle Scholar
  47. 47.
    Gebhart GF, Randich A (1990) Brainstem modulation of nociception. In: WR Klemm, RP Vertes (eds): Brainstem mechanisms of behavior. John Wiley & Sons, New York, 315–352Google Scholar
  48. 48.
    Petrov T, Krukoff TL, Jhamandas JH (1992) The hypothalamic paraventricular and lateral parabrachial nuclei receive collaterals from raphe nucleus neurons: a combined double retrograde and immunocytochemical study. J Comp Neurol 318: 18–26PubMedCrossRefGoogle Scholar
  49. 49.
    Holstege G, Tan J, Van Ham J, Bos A (1984) Mesencephalic projections to the facial nucleus in the cat. Brain Res 311: 7–22PubMedCrossRefGoogle Scholar
  50. 50.
    Tischler RC, Morin LP (2003) Reciprocal serotonergic connections between the hamster median and dorsal raphe nuclei. Brain Res 981: 126–132PubMedCrossRefGoogle Scholar
  51. 51.
    Datta S (1995) Neuronal activity in the peribrachial area: relationship to behavioral state control. Neurosci Biobehav Rev 19: 67–84PubMedCrossRefGoogle Scholar
  52. 52.
    Vertes RP (1984) Brainstem control of the events of REM sleep. Prog Neurobiol 22: 241–288PubMedCrossRefGoogle Scholar
  53. 53.
    Callaway CW, Lydic R, Baghdoyan HA, Hobson JA (1987) Ponto-geniculo-occipital waves: spontaneous visual system activity during rapid eye movement sleep. Cell Mol Neurobiol 7: 105–149PubMedCrossRefGoogle Scholar
  54. 54.
    Bobillier P, Seguin S, Degueurce A, Lewis BD, Pujol JF (1979) The efferent connections of the nucleus raphe centralis superior in the rat as revealed by radioautography. Brain Res 166: 1–8PubMedCrossRefGoogle Scholar
  55. 55.
    James MD, MacKenzie EJ, Tuohy-Jones PA, Wilson CA (1987) Dopaminergic neurones in the zona incerta exert a stimulatory control on gonadotrophin release via D1 dopamine receptors. Neuroendocrinology 45: 348–355PubMedGoogle Scholar
  56. 56.
    Morello H, Caligaris L, Haymal B, Taleisnik S (1989) Inhibition of proestrous LH surge and ovulation in rats evoked by stimulation of the medial raphe nucleus involves a GABA-mediated mechanism. Neuroendocrinology 50: 81–87PubMedGoogle Scholar
  57. 57.
    Vertes RP, Kocsis B (1997) Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 81: 893–926PubMedCrossRefGoogle Scholar
  58. 58.
    Vertes RP, Hoover WB, Viana Di Prisco G (2004) Theta rhythm of the hippocampus: subcortical control and functional significance. Behav Cogn Neurosci Rev 3: 173–200PubMedCrossRefGoogle Scholar
  59. 59.
    Assaf SY, Miller JJ (1978) Role of a raphe serotonin system in control of septal unit activity and hippocampal desynchronization. Neuroscience 3: 539–550PubMedCrossRefGoogle Scholar
  60. 60.
    Vertes RP (1981) An analysis of ascending brain stem systems involved in hippocampal synchronization and desynchronization. J Neurophysiol 46: 1140–1159PubMedGoogle Scholar
  61. 61.
    Bland BH, Colom LV (1993) Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex. Prog Neurobiol 41: 157–208PubMedCrossRefGoogle Scholar
  62. 62.
    McKenna JT, Vertes RP (2001) Collateral projections from the median raphe nucleus to the medial septum and hippocampus. Brain Res Bull 54: 619–630PubMedCrossRefGoogle Scholar
  63. 63.
    Steininger TL, Rye DB, Wainer BH (1992) Afferent projections to the cholinergic pedunculopontine tegmental nucleus and adjacent midbrain extrapyramidal area in the albino rat. I. Retrograde tracing studies. J Comp Neurol 321: 515–543PubMedCrossRefGoogle Scholar
  64. 64.
    Beitz AJ, Clements JR, Mullett MA, Ecklund LJ (1986) Differential origin of brainstem serotoninergic projections to the midbrain periaqueductal gray and superior colliculus of the rat. J Comp Neurol 250: 498–509PubMedCrossRefGoogle Scholar
  65. 65.
    Semba K (1993) Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat. J Comp Neurol 330: 543–556PubMedCrossRefGoogle Scholar
  66. 66.
    Olucha-Bordonau FE, Teruel V, Barcia-Gonzalez J, Ruiz-Torner A, Valverde-Navarro AA, Martinez-Soriano F (2003) Cytoarchitecture and efferent projections of the nucleus incertus of the rat. J Comp Neurol 464: 62–97PubMedCrossRefGoogle Scholar
  67. 67.
    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
  68. 68.
    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
  69. 69.
    Steinbusch HW (1981) Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 6: 557–618PubMedCrossRefGoogle Scholar
  70. 70.
    Parent A, Descarries L, Beaudet A (1981) Organization of ascending serotonin systems in the adult rat brain: a radioautographic study after intraventricular administration of [3H]5-hydroxytryptamine. Neuroscience 6: 115–138PubMedCrossRefGoogle Scholar
  71. 71.
    Clements JR, Beitz AJ, Fletcher TF, Mullet MA (1985) Immunocytochemical localization of serotonin in the rat periaqueductal gray: a quantitative light and electron microscopic study. J Comp Neurol 236: 60–70PubMedCrossRefGoogle Scholar
  72. 72.
    Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New YorkGoogle Scholar
  73. 73.
    Brog JS, Salyapongse A, Deutch AY, Zahm DS (1993) The patterns of afferent innervation of the core and shell in the “accumbens” part of the rat ventral striatum: immunohistochemical detection of retrogradely transported fluoro-gold. J Comp Neurol 338: 255–278PubMedCrossRefGoogle Scholar
  74. 74.
    van Bockstaele EJ, Pickel VM (1993) Ultrastructure of serotonin-immunoreactive terminals in the core and shell of the rat nucleus accumbens: cellular substrates for interactions with catecholamine afferents. J Comp Neurol 334: 603–617PubMedCrossRefGoogle Scholar
  75. 75.
    Brown P, Molliver ME (2000) Dual serotonin (5-HT) projections to the nucleus accumbens core and shell: relation of the 5-HT transporter to amphetamine-induced neurotoxicity. J Neurosci 20: 1952–1963PubMedGoogle Scholar
  76. 76.
    Vertes RP, Linley SB, Hoover WB, Hughes KM (2007) Differential serotonergic innervation of the forebrain by the dorsal (DR) and median (MR) raphe nuclei as revealed by SERT staining and selective 5-HT DR and MR lesions. Soc Neurosci Abstr, Online, Program No. 780.17Google Scholar
  77. 77.
    Hughes KM, Linley SB, Vertes, RP (2007) Effect of partial serotonergic denervation with parachloroamphetamine on reversal learning and attentional set shifting using an odor texture discrimination task in the rat. Soc Neurosci Abstr, Online, Program No. 780.16Google Scholar
  78. 78.
    Linley SB, Hoover WB, Morales GJ, Hughes KM, Vertes RP (2007) 5-HT and SERT innervation of the thalamus in the rat. Soc Neurosci Abstr, Online, Program No. 780.15Google Scholar
  79. 79.
    Mamounas LA, Molliver ME (1988) Evidence for dual serotonergic projections to neocortex: axons from the dorsal and median raphe nuclei are differentially vulnerable to the neurotoxin p-chloroamphetamine (PCA). Exp Neurol 102: 23–36PubMedCrossRefGoogle Scholar
  80. 80.
    Mamounas LA, Mullen CA, O’Hearn E, Molliver ME (1991) Dual serotoninergic projections to forebrain in the rat: morphologically distinct 5-HT axon terminals exhibit differential vulnerability to neurotoxic amphetamine derivatives. J Comp Neurol 314: 558–586PubMedCrossRefGoogle Scholar
  81. 81.
    Baumgarten HG, Bjorklund A, Lachenmayer L, Nobin A (1973) Evaluation of the effects of 5,7-dihydroxytryptamine on serotonin and catecholamine neurons in the rat CNS. Acta Physiol Scand Suppl 391: 1–19PubMedGoogle Scholar
  82. 82.
    Bjorklund A, Baumgarten HG, Nobin A (1974) Chemical lesioning of central monoamine axons by means of 5, 6-dihydroxytryptamine and 5,7-dihydroxytryptamine. Adv Biochem Psychopharmacol 10:13–33PubMedGoogle Scholar
  83. 83.
    Aghajanian GK, Wang RY (1977) Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique. Brain Res 122: 229–242PubMedCrossRefGoogle Scholar
  84. 84.
    Kalen 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
  85. 85.
    Peyron C, Petit JM, Rampon C, Jouvet M, Luppi PH (1998) Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods. Neuroscience 82: 443–468PubMedCrossRefGoogle Scholar
  86. 86.
    Lee HS, Kim MA, Valentino RJ, Waterhouse BD (2003) Glutamatergic afferent projections to the dorsal raphe nucleus of the rat. Brain Res 963: 57–71PubMedCrossRefGoogle Scholar
  87. 87.
    Jasmin L, Burkey AR, Granato A, Ohara PT (2004) Rostral agranular insular cortex and pain areas of the central nervous system: a tract-tracing study in the rat. J Comp Neurol 468: 425–440PubMedCrossRefGoogle Scholar
  88. 88.
    Hoover WB, Vertes RP (2005) Efferent projections of the insular cortex in the rat. Soc Neurosci Abstr, Online, Program No. 658.10Google Scholar
  89. 89.
    Gabbott PL, Warner TA, Jays PR, Salway P, Busby SJ (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492: 145–177PubMedCrossRefGoogle Scholar
  90. 90.
    Vertes RP (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51: 32–58PubMedCrossRefGoogle Scholar
  91. 91.
    Sesack SR, Deutch AY, Roth RH, Bunney BS (1989) Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. J Comp Neurol 290: 213–242PubMedCrossRefGoogle Scholar
  92. 92.
    Hurley KM, Herbert H, Moga MM, Saper CB (1991) Efferent projections of the infralimbic cortex of the rat. J Comp Neurol 308: 249–276PubMedCrossRefGoogle Scholar
  93. 93.
    Hajos M, Richards CD, Szekely AD, Sharp T (1998) An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat. Neuroscience 87: 95–108PubMedCrossRefGoogle Scholar
  94. 94.
    Takagishi M, Chiba T (1991) Efferent projections of the infralimbic (area 25) region of the medial prefrontal cortex in the rat: an anterograde tracer PHA-L study. Brain Res 566: 26–39PubMedCrossRefGoogle Scholar
  95. 95.
    Dong HW, Swanson LW (2006) Projections from bed nuclei of the stria terminalis, dorsomedial nucleus: Implications for cerebral hemisphere integration of neuroendocrine, autonomic, and drinking responses J Comp Neurol 494: 75–107PubMedCrossRefGoogle Scholar
  96. 96.
    Dong HW, Swanson LW (2006) Projections from bed nuclei of the stria terminalis, anteromedial area: Cerebral hemisphere integration of neuroendocrine, autonomic, and behavioral aspects of energy balance. J Comp Neurol 494: 142–178PubMedCrossRefGoogle 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.
    Zardetto-Smith AM, Johnson AK (1995) Chemical topography of efferent projections from the median preoptic nucleus to pontine monoaminergic cell groups in the rat. Neurosci Lett 199: 215–219PubMedCrossRefGoogle Scholar
  99. 99.
    Gervasoni D, Peyron C, Rampon C, Barbagli B, Chouvet G, Urbain N, Fort P, Luppi PH (2000) Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons. J Neurosci 20: 4217–4225PubMedGoogle Scholar
  100. 100.
    Sherin JE, Elmquist JK, Torrealba F, Saper CB (1998) Innervation of histaminergic tuberomammillary neurons by GABAergic and galaninergic neurons in the ventrolateral preoptic nucleus of the rat. J Neurosci 18: 4705–4721PubMedGoogle Scholar
  101. 101.
    Lu J, Bjorkum AA, Xu M, Gaus SE, Shiromani PJ, Saper CB (2002) Selective activation of the extended ventrolateral preoptic nucleus during rapid eye movement sleep. J Neurosci 22: 4568–4576PubMedGoogle Scholar
  102. 102.
    Lee HS, Kim MA, Waterhouse BD (2005) Retrograde double-labeling study of common afferent projections to the dorsal raphe and the nuclear core of the locus coeruleus in the rat. J Comp Neurol 481: 179–193PubMedCrossRefGoogle Scholar
  103. 103.
    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
  104. 104.
    Saper CB, Cano G, Scammell TE (2005) Homeostatic, circadian, and emotional regulation of sleep. J Comp Neurol 493: 92–98PubMedCrossRefGoogle Scholar
  105. 105.
    Saper CB, Scammell TE, Lu J (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature 437: 1257–1263PubMedCrossRefGoogle Scholar
  106. 106.
    Lee HS, Park SH, Song WC, Waterhouse BD (2005) Retrograde study of hyocretin-1 (orexin-A) projections to subdivisions of the dorsal raphe nucleus in the rat. Brain Res 1059: 35–45PubMedCrossRefGoogle Scholar
  107. 107.
    Lee HS, Lee BY, Waterhouse BD (2005) Retrograde study of projections from the tuberomammillary nucleus to the dorsal raphe and the locus coeruleus in the rat. Brain Res 1043: 65–75PubMedCrossRefGoogle Scholar
  108. 108.
    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
  109. 109.
    Saper CB, Swanson LW, Cowan WM (1979) An autoradiographic study of the efferent connections of the lateral hypothalamic area in the rat. J Comp Neurol 183: 689–706PubMedCrossRefGoogle Scholar
  110. 110.
    Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18: 9996–10015PubMedGoogle Scholar
  111. 111.
    Wang QP, Koyama Y, Guan JL, Takahashi K, Kayama Y, Shioda S (2005) The orexinergic synaptic innervation of serotonin-and orexin 1-receptor-containing neurons in the dorsal raphe nucleus. Regul Pept 126: 35–42PubMedCrossRefGoogle Scholar
  112. 112.
    Brown RE, Sergeeva O, Eriksson KS, Haas HL (2001) Orexin A excites serotonergic neurons in the dorsal raphe nucleus of the rat. Neuropharmacology 40: 457–459PubMedCrossRefGoogle Scholar
  113. 113.
    Takahashi K, Wang QP, Guan JL, Kayama Y, Shioda S, Koyama Y (2005) State-dependent effects of orexins on the serotonergic dorsal raphe neurons in the rat. Regul Pept 126: 43–47PubMedCrossRefGoogle Scholar
  114. 114.
    Tao R, Ma Z, McKenna JT, Thakkar MM, Winston S, Strecker RE, McCarley RW (2006) Differential effect of orexins (hypocretins) on serotonin release in the dorsal and median raphe nuclei of freely behaving rats. Neuroscience 141: 1101–1105PubMedCrossRefGoogle Scholar
  115. 115.
    Saper CB (2005) Staying awake for dinner: hypothalamic integration of sleep, feeding, and circadian rhythms. Prog Brain Res 153: 243–252Google Scholar
  116. 116.
    Fuller PM, Gooley JJ, Saper CB (2006) Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms 21: 482–493PubMedCrossRefGoogle Scholar
  117. 117.
    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
  118. 118.
    Vertes RP (1992) PHA-L analysis of projections from the supramammillary nucleus in the rat. J Comp Neurol 326: 595–622PubMedCrossRefGoogle Scholar
  119. 119.
    Vertes RP, Crane AM (1996) Descending projections of the posterior nucleus of the hypothalamus: Phaseolus vulgaris leucoagglutinin analysis in the rat. J Comp Neurol 374: 607–631PubMedCrossRefGoogle Scholar
  120. 120.
    Herkenham M, Nauta WJ (1979) Efferent connections of the habenular nuclei in the rat. J Comp Neurol 187: 19–47PubMedCrossRefGoogle Scholar
  121. 121.
    Klemm WR (2004) Habenular and interpeduncularis nuclei: shared components in multiple-function networks. Med Sci Monit 10: 261–273Google Scholar
  122. 122.
    Wang RY, Aghajanian GK (1977) Physiological evidence for habenula as major link between forebrain and midbrain raphe. Science 197: 89–91.PubMedCrossRefGoogle Scholar
  123. 123.
    Morgane PJ, Galler JR, Mokler DJ (2005) A review of systems and networks of the limbic forebrain/limbic midbrain. Prog Neurobiol 75: 143–160PubMedCrossRefGoogle Scholar
  124. 124.
    Canteras NS, Simerly RB, Swanson LW (1995) Organization of projections from the medial nucleus of the amygdala: a PHAL study in the rat. J Comp Neurol 360: 213–245PubMedCrossRefGoogle Scholar
  125. 125.
    Lee HS, Eum YJ, Jo SM, Waterhouse BD (2007) Projection patterns from the amygdaloid nuclear complex to subdivisions of the dorsal raphe nucleus in the rat. Brain Res 1143: 116–25PubMedCrossRefGoogle Scholar
  126. 126.
    Peyron C, Luppi PH, Kitahama K, Fort P, Hermann DM, Jouvet M (1995) Origin of the dopaminergic innervation of the rat dorsal raphe nucleus. Neuroreport 6: 2527–2531PubMedCrossRefGoogle Scholar
  127. 127.
    Peyron C, Luppi PH, Fort P, Rampon C, Jouvet M (1996) Lower brainstem catecholamine afferents to the rat dorsal raphe nucleus. J Comp Neurol 364: 402–413PubMedCrossRefGoogle Scholar
  128. 128.
    Kirouac GJ, Li S, Mabrouck G (2004) GABAergic projection from the ventral tegmental area and substantia nigra to the periaqueductal gray region and the dorsal raphe nucleus. J Comp Neurol 469: 170–184PubMedCrossRefGoogle Scholar
  129. 129.
    Kim MA, Less HS, Lee BY, Waterhouse BD (2004) Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat. Brain Res 1026: 56–67PubMedCrossRefGoogle Scholar
  130. 130.
    Jones BE, Moore RY (1977) Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study. Brain Res 127: 25–53PubMedGoogle Scholar
  131. 131.
    Marcinkiewicz M, Morcos R, Chretien M (1989) CNS connections with the median raphe nucleus: retrograde tracing with WGA-apoHRP-Gold complex in the rat. J Comp Neurol 289: 11–35PubMedCrossRefGoogle Scholar
  132. 132.
    Behzadi G, Kalen P, Parvopassu F, Wiklund L (1990) Afferents to the median raphe nucleus of the rat: retrograde cholera toxin and wheat germ conjugated horseradish peroxidase tracing, and selective d-[3H]aspartate labelling of possible excitatory amino acid inputs. Neuroscience 37: 77–100PubMedCrossRefGoogle Scholar
  133. 133.
    Groenewegen HJ, Berendse HW, Haber SN (1993) Organization of the output of the ventral striatopallidal system in the rat: ventral pallidal efferents. Neuroscience 57: 113–142PubMedCrossRefGoogle Scholar
  134. 134.
    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
  135. 135.
    Groenewegen HJ, Ahlenius S, Haber SN, Kowall NW, Nauta WJ (1986) Cytoarchitecture, fiber connections, and some histochemical aspects of the interpeduncular nucleus in the rat. J Comp Neurol 249: 65–102PubMedCrossRefGoogle Scholar
  136. 136.
    Satoh K, Fibiger HC (1986) Cholinergic neurons of the laterodorsal tegmental nucleus: efferent and afferent connections. J Comp Neurol 253: 277–302PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2008

Authors and Affiliations

  • Robert P. Vertes
    • 1
  • Stephanie B. Linley
    • 2
  1. 1.Center for Complex Systems and Brain SciencesFlorida Atlantic UniversityBoca RatonUSA
  2. 2.Department of PsychologyFlorida Atlantic UniversityBoca RatonUSA

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