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Sympathetic and sensory innervation of small intensely fluorescent (SIF) cells in rat superior cervical ganglion

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The sympathetic ganglion contains small intensely fluorescent (SIF) cells derived from the neural crest. We morphologically characterize SIF cells and focus on their relationship with ganglionic cells, preganglionic nerve fibers and sensory nerve endings. SIF cells stained intensely for tyrosine hydroxylase (TH), with a few cells also being immunoreactive for dopamine β-hydroxylase (DBH). Vesicular acetylcholine transporter (VAChT)-immunoreactive puncta were distributed around some clusters of SIF cells, whereas some SIF cells closely abutted DBH-immunoreactive ganglionic cells. SIF cells contained bassoon-immunoreactive products beneath the cell membrane at the attachments and on opposite sites to the ganglionic cells. Ganglion neurons and SIF cells were immunoreactive to dopamine D2 receptors. Immunohistochemistry for P2X3 revealed ramified nerve endings with P2X3 immunoreactivity around SIF cells. Triple-labeling for P2X3, TH and VAChT allowed the classification of SIF cells into three types based on their innervation: (1) with only VAChT-immunoreactive puncta, (2) with only P2X3-immunoreactive nerve endings, (3) with both P2X3-immunoreactive nerve endings and VAChT-immunoreactive puncta. The results of retrograde tracing with fast blue dye indicated that most of these nerve endings originated from the petrosal ganglion. Thus, SIF cells in the superior cervical ganglion are innervated by preganglionic fibers and glossopharyngeal sensory nerve endings and can be classified into three types. SIF cells might modulate sympathetic activity in the superior cervical ganglion.

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  1. Bairam A, Carroll JL, Labelle Y, Khandjian EW (2003) Differential changes in dopamine D2- and D1-receptor mRNA levels induced by hypoxia in the arterial chemoreflex pathway organs in one-day-old and adult rabbits.Biol Neonate 84:222–231

  2. Beaulieu J-M, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63:182–217

  3. Borghini N, Dalmaz Y, Peyrin L, Heym C (1994) Chemosensitivity, plasticity, and functional heterogeneity of paraganglionic cells in the rat coelic-superior mesenteric complex. Microsc Res Tech 29:112–119

  4. Brokaw JJ, Hansen JT (1987) Evidence that dopamine regulates norepinephrine synthesis in the rat superior cervical ganglion during hypoxic stress. J Auton Nerv Syst 18:185-193

  5. Brouns I, Oztay F, Pintelon I, De Proost I, Lembrechts R, Timmermans JP, Adriaensen D (2009) Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs. Histochem Cell Biol 131:55–74

  6. Buttigieg J, Nurse CA (2004) Detection of hypoxia-evoked ATP release from chemoreceptor cells of the rat carotid body. Biochem Biophys Res Commun 322:82–87

  7. Case CP, Matthews MR (1985) A quantitative study of structural features, synapses and nearest-neighbour relationships of small, granule-containing cells in the rat superior cervical sympathetic ganglion at various adult stages. Neuroscience 15:257–282

  8. Czyzyk-Krzeska MF, Lawson EE, Millhorn DE (1992) Expression of D2 dopamine receptor mRNA in the arterial chemoreceptor afferent pathway.J Auton Nerv Syst 41:31–39

  9. Dalmaz Y, Pequignot J-M, Tavitian E, Corttet-Emard J-P, Peyrin L (1988) Long-term hypoxia increases the turnover of dopamine but not norepinephrine in rat sympathetic ganglia. J Auton Nerv Syst 24:57–64

  10. Dalmaz Y, Borghini N, Pequignot JM, Peyrin L (1993) Presence of chemosensitive SIF cells in the rat sympathetic ganglia: a biochemical, immunocytochemical and pharmacological study. Adv Exp Med Biol 337:393-399

  11. Eränkö O (1978) Small intensely fluorescent (SIF) cells and nervous transmission in sympathetic ganglia. Ann Rev Pharmacol Toxicol 18:417–430

  12. Fan L, Guan X, Wang W, Zhao J-Y, Zhang H, Tiwari V, Hoffman PN, Li M, Tao Y-X (2014) Impaired neuropathic pain and preserved acute pain in rats overexpressing voltage-gated potassium channel subunit Kv1.2 in primary afferent neurons. Mol Pain 10:8

  13. Fidone SJ, Zapata P, Stensaas LJ (1977) Axonal transport of labeled material into sensory nerve ending of cat carotid body. Brain Res 124:9–28

  14. Fuxe K, Dahlström AB, Jonsson G, Marcellino D, Guescini M, Dam M, Manger P, Agnati L (2010) The discovery of central monoamine neurons gave volume transmission to the wired brain. Prog Neurobiol 90:82–100

  15. Hess A, Zapta P (1972) Innervation of the cat carotid body: normal and experimental studies. Fed Proc 31:1365–1382

  16. Heym C, Common B, Yin S, Klimaschewski L, Couraud J-Y, Bachmann S (1993) Neurochemistry, connectivity and plasticity of small intensely fluorescent (SIF) cells in the rat superior cervical ganglion. Ann Anat 175:309–319

  17. Heym C, Klimaschewski L, Borghini N, Fischer-Colbrie R (1994) Immunohistochemistry of small intensely fluorescent (SIF) cells and of SIF cell-associated nerve fibers in the rat superior cervical ganglion. Microsc Res Tech 29:143–150

  18. Hirakawa H, Nakamura T, Hayashida Y (1997) Effect of carbon dioxide on autonomic cardiovascular responses to systemic hypoxia in conscious rats. Am J Physiol 273:R747–R754

  19. Huang B, Zhao X, Zheng L-B, Zhang L, Ni B, Wang YW (2011) Different expression of tissue inhibitor of metalloproteinase family members in rat dorsal root ganglia and their changes after peripheral nerve injury. Neuroscience 193:421–428

  20. Huang W, Lahiri S, Mokashi A, Sherpa AK (1988) Relationship between sympathetic and phrenic nerve responses to peripheral chemoreflex in the cat. J Auton Nerv Syst 25:95–105

  21. Huang YJ, Maruyama Y, Dvoryanchikov G, Pereira E, Chaudhari N, Roper SD (2007) The role of pannexin 1 hemichannels in ATP release and cell-cell communication in mouse taste buds. Proc Natl Acad Sci U S A 104:6436–6441

  22. Huber K (2006) The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev Biol 298:335–343

  23. Itturiaga R, Alacayaga J (2004) Neurotransmission in the carotid body: transmitters and modulators between glomus cells and petrosal ganglion nerve terminals. Brain Res Rev 47:46–53

  24. Kalia M, Davies RO (1978) A neuroanatomical search for glossopharyngeal efferents to the carotid body using the retrograde transport of horseradish peroxidase. Brain Res 149:477–481

  25. Kameda Y (2014) Signaling molecules and transcription factors involved in the development of the sympathetic nervous system, with special emphasis on the superior cervical ganglion. Cell Tissue Res 357:527–548

  26. Kataoka S, Toyono T, Seta Y, Toyoshima K (2006) Expression of ATP-gated P2X3 receptors in rat gustatory papillae and taste buds. Arch Histol Cytol 69:281–288

  27. Kondo H (1977) Innervation of SIF cells in the superior cervical and nodose ganglia: an ultrastructural study with serial sections. Biol Cell 30:253–264

  28. Kummer W (1997) Innervation of paraganglia. In: Unsicker K (ed) Autonomic-endocrine interactions. Taylor & Francis, London, pp 315–356

  29. Kummer W, Neuhuber WL (1989) Vagal paragnglia of the rat. J Electron Microsc Tech 12:343–355

  30. Lahiri S, Rozanov C, Roy A, Storey B, Buerk DG (2001) Regulation of oxygen sensing in peripheral arterial chemoreceptors. Int J Biochem Cell Biol 33:755–774

  31. Libet B, Owman C (1974) Concomitant changes in formaldehyde-induced fluorescence of dopamine interneurones and in slow inhibitory post-synaptic potentials of the rabbit superior cervical ganglion, induced by stimulation of the preganglionic nerve or by a muscarinic agent. J Physiol (Lond) 237:635–662

  32. Libet B, Tosaka T (1969) Slow inhibitory and excitatory postsynaptic responses in single cells of mammalian sympathetic ganglia. J Neurophysiol 32:43–50

  33. Masson JF, Kranz C, Mizaikoff B, Gauda EB (2008) Amperometric ATP microbiosensors for the analysis of chemosensitivity at rat carotid bodies. Anal Chem 80:3991–3998

  34. Matthews MR (1989) Small, intensely fluorescent cells and the paraneuron concept. J Electron Microsc Tech 12:408–416

  35. Matthews MR, Raisman G (1969) The ultrastructure and somatic efferent synapses of small granule-containing cells in the superior cervical ganglion. J Anat 105:255–282

  36. McDonald DM (1983) Morphology of the rat carotid sinus nerve. I. Course, connections, dimensions and ultrastructure. J Neurocytol 12:345–372

  37. Moreira TS, Takakura AC, Colombari E, Guyenet PG (2006) Central chemoreceptors and sympathetic vasomotor outflow. J Physiol (Lond) 577:369–386

  38. Narushima M, Uchigashima M, Hashimoto K, Watanabe M, Kano M (2006) Deporalization-induced suppression of inhibition mediated by endocannabinoids at synapses from fast-spiking interneurons to medium spiny neurons in the striatum. Eur J Neurosci 24:2246–2252

  39. Nurse CA, Piskuric NA (2013) Signal processing at mammalian carotid body chemoreceptors. Semin Cell Dev Biol 24:22–30

  40. Piskuric NA, Vollmer C, Nurse CA (2011) Confocal immunofluorescence study of rat aortic body chemoreceptors and associated neurons in situ and in vitro. J Comp Neurol 519:856–873

  41. Prasad M, Fearon IM, Zhang M, Laing M, Vollmer C, Nurse CA (2001) Expression of P2X3 receptor subunits in rat carotid body afferent neurones: role in chemosensory signalling. J Physiol (Lond) 537:667–677

  42. Prud’homme MJ, Houdeau E, Serghini R, Tillet Y, Schemann M, Rousseau JP (1999) Small intensely fluorescent cells of the rat paracervical ganglion synthesize adrenaline, receive afferent innervation from postganglionic cholinergic neurones, and contain muscarinic receptors. Brain Res 821:141–149

  43. Roper SD (2013) Taste buds as peripheral chemosensory processors. Semin Cell Dev Biol 24:71–79

  44. Schäfer MK, Eiden LE, Weihe E (1998) Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. II. The peripheral nervous system. Neuroscience 84:361–376

  45. Schoch S, Gundelfinger ED (2006) Molecular organization of the presynaptic active zone. Cell Tissue Res 326:379–391

  46. Shtukmaster S, Schier MC, Huber K, Krispin S, Kalcheim C, Unsicker K (2013) Sympathetic neurons and chromaffin cells share a common progenitor in the neural crest in vivo. Neural Dev 8:12

  47. Uchigashima M, Narushima M, Fukaya M, Katona I, Kano M, Watanabe M (2007) Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its hysiological contribution to synaptic modulation in the striatum. J Neurosci 27:3663–3676

  48. Yang R, Montoya A, Bond A, Walton J, Kinnamon JC (2012) Immunocytochemical analysis of P2X2 in rat circumvallate taste buds. BMC Neurosci 13:51

  49. Zeidi ZF, Matthews MR (2013) Source and origin of nerve fibers immunoreactive for substance P and calcitonin gene-related peptide in the normal and chronically denervated superior cervical sympathetic ganglion of the rat. Auton Neurosci 173:28–38

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Author information

Correspondence to Yoshio Yamamoto.

Additional information

This study was partly supported by Grants-in-Aid from the Japan Society for the Promotion of Science to T.K. (25350823) and Y.Y. (22580330).

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Takaki, F., Nakamuta, N., Kusakabe, T. et al. Sympathetic and sensory innervation of small intensely fluorescent (SIF) cells in rat superior cervical ganglion. Cell Tissue Res 359, 441–451 (2015). https://doi.org/10.1007/s00441-014-2051-1

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  • Sympathetic ganglion
  • Superior cervical ganglion
  • Small intensely fluorescent cells
  • Interneuron
  • Sensory nerve ending
  • P2X3 purinoreceptor
  • Paraganglionic cells
  • Rat (Wistar)