Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1993 Feb;461:213–233. doi: 10.1113/jphysiol.1993.sp019510

Modulation of respiratory activity of neonatal rat phrenic motoneurones by serotonin.

A D Lindsay 1, J L Feldman 1
PMCID: PMC1175254  PMID: 8350262

Abstract

1. The effects of serotonin on phrenic motoneurones were studied in an in vitro preparation of the isolated brainstem and spinal cord from neonatal rats. 2. Serotonin (5-HT; > or = 5-10 microM) increased inspiratory-modulated phrenic nerve activity and produced a small amount of tonic activity during expiration. Inspiratory-modulated activity of the fourth cervical ventral root also increased, but was accompanied by robust tonic activity, which often obscured the rhythmic activity. 3. Serotonin, in both normal and tetrodotoxin-containing medium, depolarized phrenic motoneurones and increased cell input resistance. Serotonin also increased inspriatory-modulated firing as well as the response of phrenic motoneurones to injected current. The y-intercept of the relationship between firing frequency and injected current (f-I) was increased, but the slope was not affected. There was no bistable firing behaviour. 4. Under voltage clamp conditions, 5-HT produced a tonic inward current of 0.07-0.37 nA. This current increased with less negative holding potentials and decreased with more negative holding potentials (-75 to -90 mV) but did not reverse. 5. In addition, 5-HT decreased inspiratory-modulated synaptic current by 23 +/- 6%. The degree of attenuation was not affected by holding potential. The time course of the decrease in inspiratory-modulated synaptic current was similar to the changes seen in tonic inward current and input resistance. 6. Depolarization, tonic inward current, and shift in the f-I relationship produced by 5-HT were antagonized by the 5-HT2/1C receptor antagonist ketanserin and mimicked by the 5-HT2/1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). However, the 5-HT induced decrease in inspiratory-modulated synaptic current was not reduced by ketanserin nor mimicked by DOI. 7. We conclude that exogenously applied 5-HT simultaneously increases cell excitability and decreases inspiratory-modulated synaptic current in phrenic motoneurones via different types of receptors. When these responses occurred simultaneously, the increase in excitability predominated and the net effect was an augmentation of inspiratory-modulated phrenic motoneurone activity.

Full text

PDF
213

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrade R., Nicoll R. A. Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro. J Physiol. 1987 Dec;394:99–124. doi: 10.1113/jphysiol.1987.sp016862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Azmitia E. C., Whitaker-Azmitia P. M. Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. J Clin Psychiatry. 1991 Dec;52 (Suppl):4–16. [PubMed] [Google Scholar]
  3. Baskys A., Niesen C. E., Davies M. F., Carlen P. L. Modulatory actions of serotonin on ionic conductances of hippocampal dentate granule cells. Neuroscience. 1989;29(2):443–451. doi: 10.1016/0306-4522(89)90071-7. [DOI] [PubMed] [Google Scholar]
  4. Berger A. J., Takahashi T. Serotonin enhances a low-voltage-activated calcium current in rat spinal motoneurons. J Neurosci. 1990 Jun;10(6):1922–1928. doi: 10.1523/JNEUROSCI.10-06-01922.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bobker D. H., Williams J. T. Ion conductances affected by 5-HT receptor subtypes in mammalian neurons. Trends Neurosci. 1990 May;13(5):169–173. doi: 10.1016/0166-2236(90)90042-9. [DOI] [PubMed] [Google Scholar]
  6. Bobker D. H., Williams J. T. Serotonin agonists inhibit synaptic potentials in the rat locus ceruleus in vitro via 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors. J Pharmacol Exp Ther. 1989 Jul;250(1):37–43. [PubMed] [Google Scholar]
  7. Colino A., Halliwell J. V. Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature. 1987 Jul 2;328(6125):73–77. doi: 10.1038/328073a0. [DOI] [PubMed] [Google Scholar]
  8. Hicks T. P., Krupa M., Crépel F. Selective effects of serotonin upon excitatory amino acid-induced depolarizations of Purkinje cells in cerebellar slices from young rats. Brain Res. 1989 Jul 17;492(1-2):371–376. doi: 10.1016/0006-8993(89)90922-0. [DOI] [PubMed] [Google Scholar]
  9. Holtman J. R., Jr, Dick T. E., Berger A. J. Involvement of serotonin in the excitation of phrenic motoneurons evoked by stimulation of the raphe obscurus. J Neurosci. 1986 Apr;6(4):1185–1193. doi: 10.1523/JNEUROSCI.06-04-01185.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holtman J. R., Jr, Dick T. E., Berger A. J. Serotonin-mediated excitation of recurrent laryngeal and phrenic motoneurons evoked by stimulation of the raphe obscurus. Brain Res. 1987 Aug 4;417(1):12–20. doi: 10.1016/0006-8993(87)90174-0. [DOI] [PubMed] [Google Scholar]
  11. Hounsgaard J., Hultborn H., Jespersen B., Kiehn O. Bistability of alpha-motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan. J Physiol. 1988 Nov;405:345–367. doi: 10.1113/jphysiol.1988.sp017336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hounsgaard J., Kiehn O. Serotonin-induced bistability of turtle motoneurones caused by a nifedipine-sensitive calcium plateau potential. J Physiol. 1989 Jul;414:265–282. doi: 10.1113/jphysiol.1989.sp017687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jackson D. A., White S. R. Receptor subtypes mediating facilitation by serotonin of excitability of spinal motoneurons. Neuropharmacology. 1990 Sep;29(9):787–797. doi: 10.1016/0028-3908(90)90151-g. [DOI] [PubMed] [Google Scholar]
  14. Jacobs B. L. Serotonin and behavior: emphasis on motor control. J Clin Psychiatry. 1991 Dec;52 (Suppl):17–23. [PubMed] [Google Scholar]
  15. Joëls M., Shinnick-Gallagher P., Gallagher J. P. Effect of serotonin and serotonin analogues on passive membrane properties of lateral septal neurons in vitro. Brain Res. 1987 Aug 4;417(1):99–107. doi: 10.1016/0006-8993(87)90183-1. [DOI] [PubMed] [Google Scholar]
  16. Kelly J. S., Larkman P., Penington N. J., Rainnie D. G., McAllister-Williams H., Hodgkiss J. Serotonin receptor heterogeneity and the role of potassium channels in neuronal excitability. Adv Exp Med Biol. 1991;287:177–191. doi: 10.1007/978-1-4684-5907-4_15. [DOI] [PubMed] [Google Scholar]
  17. Lalley P. M. Responses of phrenic motoneurones of the cat to stimulation of medullary raphe nuclei. J Physiol. 1986 Nov;380:349–371. doi: 10.1113/jphysiol.1986.sp016290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lalley P. M. Serotoninergic and non-serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat. J Physiol. 1986 Nov;380:373–385. doi: 10.1113/jphysiol.1986.sp016291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Larkman P. M., Penington N. J., Kelly J. S. Electrophysiology of adult rat facial motoneurones: the effects of serotonin (5-HT) in a novel in vitro brainstem slice. J Neurosci Methods. 1989 May;28(1-2):133–146. doi: 10.1016/0165-0270(89)90018-6. [DOI] [PubMed] [Google Scholar]
  20. Leger L., Descarries L. Serotonin nerve terminals in the locus coeruleus of adult rat: a radioautographic study. Brain Res. 1978 Apr 21;145(1):1–13. doi: 10.1016/0006-8993(78)90791-6. [DOI] [PubMed] [Google Scholar]
  21. Lindsay A. D., Greer J. J., Feldman J. L. Phrenic motoneuron morphology in the neonatal rat. J Comp Neurol. 1991 Jun 8;308(2):169–179. doi: 10.1002/cne.903080204. [DOI] [PubMed] [Google Scholar]
  22. Liu G., Feldman J. L., Smith J. C. Excitatory amino acid-mediated transmission of inspiratory drive to phrenic motoneurons. J Neurophysiol. 1990 Aug;64(2):423–436. doi: 10.1152/jn.1990.64.2.423. [DOI] [PubMed] [Google Scholar]
  23. Lorenzon N. M., Foehring R. C. Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons. J Neurophysiol. 1992 Feb;67(2):350–363. doi: 10.1152/jn.1992.67.2.350. [DOI] [PubMed] [Google Scholar]
  24. Maura G., Barzizza A., Folghera S., Raiteri M. Release of endogenous aspartate from rat cerebellum slices and synaptosomes: inhibition mediated by a 5-HT2 receptor and by a 5-HT1 receptor of a possibly novel subtype. Naunyn Schmiedebergs Arch Pharmacol. 1991 Mar;343(3):229–236. doi: 10.1007/BF00251120. [DOI] [PubMed] [Google Scholar]
  25. Morin D., Hennequin S., Monteau R., Hilaire G. Serotonergic influences on central respiratory activity: an in vitro study in the newborn rat. Brain Res. 1990 Dec 10;535(2):281–287. doi: 10.1016/0006-8993(90)91611-j. [DOI] [PubMed] [Google Scholar]
  26. Morin D., Monteau R., Hilaire G. Compared effects of serotonin on cervical and hypoglossal inspiratory activities: an in vitro study in the newborn rat. J Physiol. 1992;451:605–629. doi: 10.1113/jphysiol.1992.sp019181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Morin D., Monteau R., Hilaire G. Serotonin and cervical respiratory motoneurones: intracellular study in the newborn rat brainstem-spinal cord preparation. Exp Brain Res. 1991;84(1):229–232. doi: 10.1007/BF00231779. [DOI] [PubMed] [Google Scholar]
  28. Nagano N., Ono H., Fukuda H. Functional significance of subtypes of 5-HT receptors in the rat spinal reflex pathway. Gen Pharmacol. 1988;19(6):789–793. [PubMed] [Google Scholar]
  29. North R. A., Uchimura N. 5-Hydroxytryptamine acts at 5-HT2 receptors to decrease potassium conductance in rat nucleus accumbens neurones. J Physiol. 1989 Oct;417:1–12. doi: 10.1113/jphysiol.1989.sp017786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Panicker M. M., Parker I., Miledi R. Receptors of the serotonin 1C subtype expressed from cloned DNA mediate the closing of K+ membrane channels encoded by brain mRNA. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2560–2562. doi: 10.1073/pnas.88.6.2560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Salzman S. K., Hirofuji E., Llados-Eckman C., MacEwen G. D., Beckman A. L. Monoaminergic responses to spinal trauma. Participation of serotonin in posttraumatic progression of neural damage. J Neurosurg. 1987 Mar;66(3):431–439. doi: 10.3171/jns.1987.66.3.0431. [DOI] [PubMed] [Google Scholar]
  32. Schmid K., Böhmer G., Merkelbach S. Serotonergic control of phrenic motoneuronal activity at the level of the spinal cord of the rabbit. Neurosci Lett. 1990 Aug 14;116(1-2):204–209. doi: 10.1016/0304-3940(90)90411-2. [DOI] [PubMed] [Google Scholar]
  33. Smith J. C., Feldman J. L. In vitro brainstem-spinal cord preparations for study of motor systems for mammalian respiration and locomotion. J Neurosci Methods. 1987 Oct;21(2-4):321–333. doi: 10.1016/0165-0270(87)90126-9. [DOI] [PubMed] [Google Scholar]
  34. Takahashi T., Berger A. J. Direct excitation of rat spinal motoneurones by serotonin. J Physiol. 1990 Apr;423:63–76. doi: 10.1113/jphysiol.1990.sp018011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Takahashi T. Inward rectification in neonatal rat spinal motoneurones. J Physiol. 1990 Apr;423:47–62. doi: 10.1113/jphysiol.1990.sp018010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vu E. T., Krasne F. B. Evidence for a computational distinction between proximal and distal neuronal inhibition. Science. 1992 Mar 27;255(5052):1710–1712. doi: 10.1126/science.1553559. [DOI] [PubMed] [Google Scholar]
  37. Wallis D. I., Connell L. A., Kvaltinova Z. Further studies on the action of 5-hydroxytryptamine on lumbar motoneurones in the rat isolated spinal cord. Naunyn Schmiedebergs Arch Pharmacol. 1991 Apr;343(4):344–352. doi: 10.1007/BF00179038. [DOI] [PubMed] [Google Scholar]
  38. Wallén P., Buchanan J. T., Grillner S., Hill R. H., Christenson J., Hökfelt T. Effects of 5-hydroxytryptamine on the afterhyperpolarization, spike frequency regulation, and oscillatory membrane properties in lamprey spinal cord neurons. J Neurophysiol. 1989 Apr;61(4):759–768. doi: 10.1152/jn.1989.61.4.759. [DOI] [PubMed] [Google Scholar]
  39. Wang M. Y., Dun N. J. 5-Hydroxytryptamine responses in neonate rat motoneurones in vitro. J Physiol. 1990 Nov;430:87–103. doi: 10.1113/jphysiol.1990.sp018283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wu S. Y., Wang M. Y., Dun N. J. Serotonin via presynaptic 5-HT1 receptors attenuates synaptic transmission to immature rat motoneurons in vitro. Brain Res. 1991 Jul 19;554(1-2):111–121. doi: 10.1016/0006-8993(91)90178-x. [DOI] [PubMed] [Google Scholar]
  41. Zhan W. Z., Ellenberger H. H., Feldman J. L. Monoaminergic and GABAergic terminations in phrenic nucleus of rat identified by immunohistochemical labeling. Neuroscience. 1989;31(1):105–113. doi: 10.1016/0306-4522(89)90033-x. [DOI] [PubMed] [Google Scholar]
  42. Zhang L. Effects of 5-hydroxytryptamine on cat spinal motoneurons. Can J Physiol Pharmacol. 1991 Feb;69(2):154–163. doi: 10.1139/y91-022. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES