Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris leucoagglutinin

Luppi P.H., Aston-Jones G., Akaoka H., Chouvet and Jouvet M.
Neuroscience (1995) Vol:65 Tome:1 pp:119-160
TABLE OF CONTENTS

Introduction

Material and methods

RESULTS

I. Cytoarchitecture of the locus coeruleus area

II. Afferent projections to the locus coeruleus

A) Retrograde tracing experiments

B) Anterograde tracing experiments

Discussion

FIGURES

Results

I. Cytoarchitecture of the Locus Coeruleus area

The cytoarchitecture of the LC area has been described previously 25, 53, 60, 66. Nevertheless, in the course of our study of LC afferents, we found additional undefined landmarks in this area. To study the organization of the LC area, 20µm frontal LC sections taken every 100µm from control rat brains were stained with neutral red and mounted in rostro-caudal order. At its more caudal tip, the LC is separated medially from the fourth ventricle by a 30µm thick cell poor lamina and the 20 µm thick ependyma. Laterally and ventrally, the nucleus is bordered by the MVe. Dorsally, the LC is bordered by the brachium conjunctivum (Fig. 2F) . Slightly rostrally, the medially located cell poor lamina is thicker (approximately 100µm) and the 5Me appears laterally. At this level, the 5Me is separated from the LC by an area containing few cells in white matter (Fig. A HREF="../figures/fig2b.php">2B) that appears to be a rostral extension of the MVe. Slightly more rostrally, at the level of the maximum extension of the LC, this region becomes thinner and the 5Me is very close to the lateral border of the LC. Medially, the LC is separated from the ventricle by a large undefined area that appears to be part of the pontine periaqueductal gray. At this level and more rostrally, the LC is bordered dorsally by the medial parabrachial nucleus (Fig. 3C). More rostrally, the ventral part of the LC progressively becomes less compact and then disappears and only a dorsal collection of LC cells remains (Fig. 3C). Ventral to them, two groups of cells appear with a morphology distinct from the adjacent periaqueductal gray. One is located just ventral to the few LC cells and medial to the 5Me and is composed of small ovoid cells. The second is located more medially and ventrally and is composed of slightly larger ovoid cells. The first group has not been previously defined. Therefore, because of its localization just medial to the 5Me, we denote this as the Peri-5Me nucleus (Fig. 3C). The second group of cells corresponds to t he previously defined Barrington's nucleus (Bar) 8,59. With regard to the LC noradrenergic neurons, it is noteworthy that a large number of processes (apparently dendrites) were found outside the nuclear core of the LC in select peri-LC regions, particularly in the lamina between the LC and the fourth ventricle and also in the a reas rostromedial and caudodorsal to the LC nucleus proper. Note that LC dendrites did not appear to be extensive lateral to the LC nucleus proper. This topographically specific distribution of presumed LC dendrites is similar to that previously reported in a more extensive analysis 22,61.

Next page

REFERENCES
  1. Allen G.V. and Cechetto D.F. (1992) Functional and anatomical organization of cardio vascular pressor and depressor sites in the lateral hypothalamic area: I. Descending projections. J.Comp.Neurol. 315, 313-332.
  2. Astier B., Kitahama K., Denoroy L., Jouvet M. and Renaud B. (1987) Immunohistochemical evidence for the adrenergic medullary longitudinal bundle as a major ascending pathway to the locus coeruleus. Neurosci.Lett. 74, 132-138.
  3. Aston-Jones G., Astier B. and Ennis M. (1992) Inhibition of locus coeruleus noradrenergic neurons by C1 adrenergic cells in the rostral ventral medulla. Neuroscience 48, 371-382.
  4. Aston-Jones G. and Bloom F.E. (1981) Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J.Neurosci. 1, 876-886.
  5. Aston-Jones G. and Bloom F.E. (1981) Norepinephrine containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. J.Neurosci. 8, 887-900.
  6. Aston-Jones G., Ennis M., Pieribone V.A., Nickell W.T. and Shipley M.T. (1986) The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science 234, 734-737.
  7. Aston-Jones, G., Shipley, M.T., Chouvet, G., et al. Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. In: Progress in brain research, Vol 88, edited by Barnes, C.D. and Pompeiano, O. Amsterdam: Elsevier, 1991, p. 47-75.
  8. Barrington F.J.F. (1925) The effect of lesions of the hind- and midbrain on micturition in the cat. Quart. J. Exp. Physiol. 15, 81-102.
  9. Buda, M., Akaoka, H., Aston-Jones, G., et al. Modulation of locus coeruleus activity by serotoninergic afferents. In: Serotonin, the Cerebellum, and Ataxia, edited by Trouillas, P. and Fuxe, K. New York: Raven Press, Ltd, 1993, p. 237-253.
  10. Cedarbaum J.M. and Aghajanian G.K. (1978) Afferent projections to the rat locus coeruleus as determined by a retrograde tracing technique. J.Comp.Neurol. 178, 1-16.
  11. Chase M.H., Soja P.J. and Morales F.R. (1989) Evidence that glycine mediates the postsynaptic potentials that inhibit lumbar motoneurons during the atonia of active sleep. J.Neurosci. 9, 743-751.
  12. Chiang C., Ennis M., Pieribone V.A. and Aston-Jones G. (1987) Effects of prefrontal cortex stimulation on locus coeruleus discharge. Abstr.Soc.Neurosci. 13, 912.
  13. Clavier R.M. (1979) Afferent projections to the self-stimulation regions of the dorsal pons, including the locus coeruleus, in the rat as demonstrated by the horseradish peroxidase technique. Brain Res.Bull. 4, 497-504.
  14. Conrad L.C.A., Leonard C.M. and Pfaff D.W. (1974) Connections of the median and dorsal raphe nuclei in the rat: an autoradiographic and degeneration study. J.Comp.Neurol. 156, 179-206.
  15. Conrad L.C.A. and Pfaff D.W. (1976) Efferents from medial basal forebrain and hypothalamus in the rat I. An autoradiographic study of the medial preoptic area. J.Comp.Neurol. 169, 185-220.
  16. Dahlström A. and Fuxe K. (1964) Evidence for the existence of monoamine neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol.Scand.(Suppl.232) 62, 1-55.
  17. Datta S., Calvo J.M., Quattrochi J. and Hobson J.A. (1991) Long-term enhancement of REM sleep following cholinergic stimulation. Neuroreport 2, 619-622.
  18. Drolet G., Van Bockstaele E.J. and Aston-Jones G. (1992) Robust enkephalin innervation of the locus coeruleus from the rostral medulla. J.Neurosci. 12, 3162-3174.
  19. Ennis M. and Aston-Jones G. (1989) Potent inhibitory input to locus coeruleus from the nucleus prepositus hypoglossi. Brain Res.Bull. 22, 793-803.
  20. Ennis M. and Aston-Jones G. (1989) GABA-mediated inhibition of locus coeruleus from the dorsomedial rostral medulla. J.Neurosci. 9, 2973-2981.
  21. Ennis M., Behbehani M., Shipley M.T., Van Bockstaele E.J. and Aston-Jones G. (1991) Projections from the periaqueductal gray to the rostromedial pericoerulear region and nucleus locus coeruleus: anatomic and physiologic studies. J.Comp.Neurol. 306, 480-494.
  22. Fu L., Shipley M.T. and Aston-Jones G. (1989) Dendrites of rat locus coeruleus are asymmetrically distributed: Immunocytochemical LM and EM studies. Abstr.Soc.Neurosci. 15, 1013.
  23. Fung S.J., Reddy V.K., Bowker R.M. and Barnes C.D. (1987) Differential labeling of the vestibular complex following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus. Brain Res. 401, 347-352.
  24. Gerfen C.R. and Sawchenko P.E. (1984) An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: Immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L). Brain Res. 290, 219-238.
  25. Groves P.M. and Wilson C.J. (1980) Fine structure of rat locus coeruleus. J.Comp.Neurol. 193, 841-852.
  26. Grzanna R. and Molliver M.E. (1980) The locus coeruleus in the rat: an immunohistochemical delineation. Neuroscience 5, 21-40.
  27. Herbert H., Moga M.M. and Saper C.B. (1990) Connections of the parabrachialis nucleus with the nucleus of the solitary tract and the medullary reticular formation. J.Comp.Neurol. 293, 540-580.
  28. Herkenham M. and Nauta W.J. (1979) Efferent connections of the habenular nuclei in the rat. J.Comp.Neurol. 187, 19-47.
  29. Hobson J.A., McCarley R.W. and Wyzinski P.W. (1975) Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 189, 55-58.
  30. Hosoya Y. and Matsushita M. (1981) Brainstem projections from the lateral hypothalamic area in the rat, as studied with autoradiography. Neurosci.Lett. 24, 111-116.
  31. Hsu S., Raine L. and Fanger H. (1981) A comparative study of the peroxydase-antiperoxydase method and an avidin-biotin complex method for studying polypeptides hormones with radioimmunoassay antibodies. A.J.Clin.Pathol. 75, 734-738.
  32. Hurley K.M., Herbert H., Moga M.M. and Saper C.B. (1991) efferent projections of the infralimbic cortex of the rat. J.Comp.Neurol. 308, 249-276.
  33. Jones, B.E. Noradrenergic locus coeruleus neurons: their distant connections and their relationship to neighboring (including cholinergic and GABAergic) neurons of the central gray and reticular formation. In: Progress in brain research, vol 88, edited by Barnes, C.D. and Pompeiano, O. Amsterdam: Elsevier, 1991, p. 15-29.
  34. Jouvet M. (1962) Recherches sur les structures nerveuses et les mécanismes responsables des différentes phases du sommeil physiologique. Arch.Ital.Biol. 100, 125-206.
  35. Kachidian P., Astier B., Renaud B. and Bosler O. (1990) Adrenergic innervation of noradrenergic locus coeruleus neurons. A dual labeling immunocytochemical study in the rat. Neurosci.Lett. 109, 23-29.
  36. Krieger M.S., Conrad L.C.A. and Pfaff D.W. (1979) An autoradiographic study of the efferent connections of the ventromedial nucleus of the hypothalamus. J.Comp.Neurol. 183, 785-816.
  37. Leger L., Degueurce A.M. and Pujol J.F. (1980) (Origin of the serotoninergic innervation of the rat locus coeruleus) Origine de l'innervation serotoninergique du locus coeruleus chez le rat. C.R.Acad.Sci.D. 290, 807-810.
  38. Luiten P.G.M., Ter Horst G.J. and Steffens A.B. (1987) The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism. Prog.Neurobiol. 1-54.
  39. Luppi P.H., Aston-Jones G., Akaoka H., Charléty P., Kowelowsky C., Shipley M.T., Zhu Y., Ennis M., Fort P., Chouvet G. and Jouvet M. (1991) Afferents to the rat locus coeruleus (LC) using choleratoxin B subunit (CTb) as a retrograde tracer. Abstr.Soc.Neurosci. 17, 1540.
  40. Luppi P.H., Charléty P.J., Fort P., Akaoka H., Chouvet G. and Jouvet M. (1991) Anatomical and electrophysiological evidence for a glycinergic inhibitory innervation of the rat locus coeruleus. Neurosci.Lett. 128, 33-36.
  41. Luppi P.H., Fort P. and Jouvet M. (1990) Iontophoretic application of unconjugated cholera toxin B subunit (CTb) combined with immunohistochemistry of neurochemical substances: a method for transmitter identification of retrogradely labeled neurons. Brain Res. 534, 209-224.
  42. Machado B.H. and Brody M.J. (1988) Role of the nucleus ambiguus in the regulation of heart rate and arterial pressure. Hypertension 11, 602-607.
  43. McCarley R.W. and Hobson J.A. (1975) Neuronal excitability modulation over the sleep cycle: a structural and mathematical model. Science 189, 58-60.
  44. Moga M.M., Herbert H., Hurley K.M., Yasui Y., Gray T.S. and Saper C.B. (1990) Organization of cortical, basal forebrain, and hypothalamic afferents to the parabrachial nucleus in the rat. J.Comp.Neurol. 295, 624-661.
  45. Morgane P.J. and Jacobs M.S. (1979) Raphe projections to the locus coeruleus in the rat. Brain Res.Bull. 4, 519-534.
  46. 4North R.A. and Williams J.T. (1985) On the potassium conductance increased by opioids in rat locus coeruleus neurons. J.Physiol.(London) 364, 265-280.
  47. Panula P., Pirvola U., Auvinen S. and Airaksinen M.S. (1989) Histamine-immunoreactive nerve fibers in the rat brain. Neuroscience 28, 585-610.
  48. Panula P., Yang H.Y.T. and Costa E. (1984) Histamine-containing neurons in the rat hypothalamus. Proc.Natn.Acad.Sci.U.S.A. 81, 2572-2576.
  49. Paxinos, G. and Watson, C. The rat brain in stereotaxic coordinates, Sidney:Academic Press, 1986. Ed. 2
  50. Pieribone V.A. and Aston-Jones G. (1991) Adrenergic innervation of the rat nucleus locus coeruleus arises predominantly from the C1 adrenergic cell group in the rostral medulla. Neuroscience 41, 525-542.
  51. Pieribone V.A., Aston-Jones G. and Bohn M.C. (1988) Adrenergic and non-adrenergic neurons in the C1 and C3 areas project to locus coeruleus: a fluorescent double labeling study. Neurosci.Lett. 85, 297-303.
  52. Pieribone V.A., Van Bockstaele E.J., Shipley M.T. and Aston-Jones G. (1989) Serotonergic innervation of rat locus coeruleus derives from non-raphe brain areas. Abstr.Soc.Neurosci. 15, 420.
  53. Rizvi T.A., Ennis M., Aston-Jones G., Maorong J. and Shipley M.T. (1994) Preoptic projections to Barrington's nucleus and the peri-coerulear region column: Architecture and terminal organization. J.Comp.Neurol. In Press,
  54. Robertson B. and Grant G. (1985) A comparison between wheat germ agglutinin- and choleragenoid-horseradish peroxidase as anterogradely transported markers in central branches of primary sensory neurones in the rat with some observations in the cat. Neuroscience 14, 895-905.
  55. Ruggiero D.A., Giulano R., Anwar M., Stornetta R. and Reis D.J. (1990) Anatomical substrates of cholinergic-autonomic regulation in the rat. J.Comp.Neurol. 292, 1-53.
  56. Sakai, K. Anatomical and physiological basis of paradoxal sleep. In: , edited by Drucker-Colin, R., McGinty, D.J., Morrisson, A. and Parmeggiani, L. New York: Raven Press, 1985, p. 111-137.
  57. Sakai K., Touret M., Salvert D., Leger L. and Jouvet M. (1977) Afferent projections to the cat locus coeruleus as visualized by the horseradish peroxidase technique. Brain Res. 119, 21-41.
  58. Saper C.B., Swanson L.W. and Cowan W.M. (1976) The efferent connections of the ventromedial nucleus of the hypothalamus of the rat. J.Comp.Neurol. 169, 409-442.
  59. Satoh K., Shimizu N., Tohyama M. and Maeda T. (1978) Localization of the micturation reflex center at the dorsolateral pontine tegmentum of the rat. Neurosci.Lett. 8, 27-33.
  60. Shimizu N., Katoh Y., Hida T. and Satoh K. (1979) The fine structural organization of the locus coeruleus in the rat with reference to noradrenaline contents. Exp.Brain Res. 37, 139-148.
  61. Shipley M.T., Fu L., Ennis M. and Aston-Jones G. (1994) Distribution of locus coeruleus extranuclear dendrites. Immunocytochemical LM and EM studies. J.Comp.Neurol. submitted,
  62. Shirokawa T. and Nakamura S. (1987) Antidromic activation of rat dorsomedial hypothalamic neurons from locus coeruleus and median eminence. Brain Res.Bull. 18, 291-295.
  63. Simerly R.B. and Swanson L.W. (1988) Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J.Comp.Neurol. 270, 209-242.
  64. Simon H., Le Moal M., Stinus L. and Calas A. (1979) Anatomical relationships between the ventral mesencephalic tegmentum-A10 region and the locus coeruleus as demonstrated by anterograde and retrograde tracing techniques. J.Neural.Transm. 44, 77-86.
  65. Somogyi P., Minson J.B., Morilak D.A., Llevewellyn-Smith I., McIlhinney J.R.A. and Chalmers J. (1989) Evidence for an excitatory amino acid pathway in the brainstem and for its involvement in cardiovascular control. Brain Res. 496, 401-407.
  66. Swanson L.W. (1976) The locus coeruleus: a cytoarchitectonic, Golgi and immunohistochemical study in the albino rat. Brain Res. 110, 39-56.
  67. Swanson L.W. (1976) An autoradiographic study of the efferent connections of the preoptic region in the rat. J.Comp.Neurol. 167, 227-256.
  68. Takagishi M. and 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, 26-39.
  69. Van der Kooy D., Koda L.Y., McGinty J.F., Gerfen C.R. and Bloom F.E. (1984) The organization of projections from the cortex, amygdala, and hypothalamus to the nucleus of the solitary tract in rat. J.Comp.Neurol. 224, 1-24.
  70. Villalobos J. and Ferssiwi A. (1987) The differential descending projections from the anterior, central and posterior regions of the lateral hypothalamic area: an autoradiographic study. Neurosci.Lett. 81, 95-99.
  71. Williams J.T., North R.A., Shefner S.A., Nishi S. and Egan T.M. (1984) Membrane properties of rat locus coeruleus neurones. Neuroscience 13, 137-156.
  72. Yasui Y., Breder C.D., Saper C.B. and Cechetto D.F. (1991) Autonomic responses and efferent pathways from the insular cortex in the rat. J.Comp.Neurol. 303, 355-374.