Skip to main content
Cellular and Molecular Neurobiology logoLink to Cellular and Molecular Neurobiology
. 2003 Oct;23(4-5):665–680. doi: 10.1023/A:1025040600812

Modulatory Inputs on Sympathetic Neurons in the Rostral Ventrolateral Medulla in the Rat

Antonio R Granata 1,
PMCID: PMC11530172  PMID: 14514023

Abstract

1. The first part of this study looks at spontaneously active neurons located in the rostral ventrolateral medulla (RVLM) with projections to the thoracic spinal cord. Sixteen neurons were intracellularly recorded in vivo. Four out of 16 neurons were antidromically activated from the thoracic spinal cord (axonal conduction velocities varied from 1.8 m/s to 9.5 m/s).

2. The simultaneous averages of the neuronal membrane potential and arterial blood pressure triggered by the pulsatile arterial wave or the EKG-R wave demonstrated changes in membrane potential (hyperpolarization or depolarization) locked to the cardiac cycle in four neurons in this group. These neurons (three of them bulbospinal) were further tested for barosensitivity by characterizing the responses to electrical stimulation of the aortic depressor nerve. Four neurons responded with inhibitory hyperpolarizing responses characterized as inhibitory postsynaptic potentials (IPSP) to aortic nerve stimulation (onset latency: 32.3 ± 5.0 ms; mean ± SEM).

3. In two neurons in the RVLM, one of them characterized as barosensitive, electrical stimulation of the opposite RVLM (0.5 Hz, 1.0 ms pulse duration, 25–100 μA) elicited excitatory postsynaptic potentials (EPSPs) with latencies of 9.07 and 10.5 ms. At resting membrane potential, the onset latency of the evoked EPSPs did not change with increasing stimulus intensities. Some of the recorded neurons were intracellularly labelled with biocytin for visualization. They were found in the RVLM.

4. These experiments in vivo would support the idea of a functional commissural pathway between the RVLM of both sides.

5. Anatomical data have shown that some of those commissural bundle fibers originate in the C1 adrenergic neuronal group in the RVLM. In the second part of this study, we used an intracellular recording technique in vitro to investigate the effects of the indirect adrenergic agonist tyramine on neurons in the RVLM with electrophysiological properties similar to premotor sympathetic neurons in vivo.

6. Tyramine (0.5–1 mM) produced a pronounced inhibitory effect with hyperpolarization and increase in membrane input resistance on two neurons characterized as regularly firing (R), and on one neuron characterized as irregularly firing (I). This effect was preceded by a transient depolarization with increases in firing rate.

7. These results would indicate that neurons in the RVLM recorded in vitro and with properties similar to premotor sympathetic neurons can be modulated by catecholamines released from terminals probably making synaptic contacts.

Keywords: rostral ventrolateral medulla, commissural pathway, intracellular recording, EPSP/IPSP, sympathetic premotor neurons, sympathetic tone, tyramine

REFERENCES

  1. Alexander, R. W., Davis, J. N., and Lefkowitz, R. J. (1975). Direct identification and characterization of β-adrenergic receptors in rat brain. Nature (Lond.)258:437–440. [DOI] [PubMed] [Google Scholar]
  2. Allen, A. M., and Guyenet, P. G. (1993). α2-Adrenoceptor-mediated inhibition of bulbospinal barosensitive cells of rat rostral medulla. Am. J. Physiol. 265(34):R1065-R1075. [DOI] [PubMed] [Google Scholar]
  3. Ellenberger, H. H., and Feldman, J. L. (1990). Subnuclear organization of the lateral tegmental field of the rat: I. Nucleus ambiguous and ventral respiratory group. J. Comp. Neurol. 294:202–211. [DOI] [PubMed] [Google Scholar]
  4. Granata, A. R. (2001). Effects of γ-aminobutyric acid on putative sympathoexcitatory neurons in the rat rostral ventrolateral medulla in vitro. Intracellular study. Neurosci. Lett. 300:49–53. [DOI] [PubMed] [Google Scholar]
  5. Granata, A. R., and Chang, H. T. (1994). Relationship of calbindin-D28k with afferent neurons to the rostral ventrolateral medulla in the rat. Brain Res. 645:265–277. [DOI] [PubMed] [Google Scholar]
  6. Granata, A. R., and Cohen, M. I. (2002). Rhythmic properties of neurons in the rostral ventrolateral medulla of the rat in vitro: Effects of clonidine. J. Neurophysiol. 88:2262–2279. [DOI] [PubMed] [Google Scholar]
  7. Granata, A. R., and Kitai, S. T. (1992). Intracellular analysis in vivo of different barosensitive bulbospinal neurons in the rat rostral ventrolateral medulla. J. Neurosci. 12:1–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Granata, A. R, Numao, Y., Kumada, M., and Reis, D. J. (1986). A1 noradrenergic neurons tonically inhibit sympathoexcitatory neurons of C1 area in rat brain stem. Brain Res. 377:127–146. [DOI] [PubMed] [Google Scholar]
  9. Granata, A. R., and Reis, D. J. (1987). Hypotension and bradycardia elicited by histamine into the C1 area of the rostral ventrolateral medulla. Eur. J. Pharmacol. 136:157–162. [DOI] [PubMed] [Google Scholar]
  10. Granata, A. R., and Ruggiero, D. A. (1998). Evidence of disynaptic projections from the rostral ventrolateral medulla to the thoracic spinal cord. Brain Res. 781:329–334. [DOI] [PubMed] [Google Scholar]
  11. Granata, A. R., Ruggiero, D. A., Park, D. H., Joh, T. H., and Reis, D. J. (1985). Brain stem area with C1-epinephrine neurons mediates baroreflex vasodepressor responses. Am. J. Physiol. 248(17):H547-H567. [DOI] [PubMed] [Google Scholar]
  12. Hayar, A., Feltz, P., and Piguet, P. (1997). Adrenergic responses in silent and putative inhibitory pacemaker-like neurons of the rat rostral ventrolateral medulla in vitro. Neuroscience77:199–217. [DOI] [PubMed] [Google Scholar]
  13. Huang, W. X., Yu, Q., and Cohen, M. I. (2000). Fast (3 Hz and 10 Hz) and slow (respiratory) rhythms in cervical sympathetic nerve and units discharges of the cat. J. Physiol. (Lond.)523:459–477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kangrga, I. M., and Loewy, A. D. (1995). Whole-cell recordings from visualized C1 adrenergic bulbospinal neurons: Ionic mechanisms underlying vasomotor tone. Brain Res. 670:215–232. [DOI] [PubMed] [Google Scholar]
  15. Lewis, D. I., and Coote, J. H. (1993). The actions of 5-hydroxytryptamine on the membrane of putative sympatho-excitatory neurons in the rostral ventrolateral medulla of the adult rat in vitro. Brain Res. 609:103–109. [DOI] [PubMed] [Google Scholar]
  16. Link, R. E., Desai, K., Hein, L., Stevens, M. E., Chruscinski, A., Bernstein, D., Barsh, G. S., and Kobilka, B. K. (1996). Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Science273:803–805. [DOI] [PubMed] [Google Scholar]
  17. MacMillan, L. B., Hein, L., Smith, M. S., Piascik, M. T., and Limbird, L. E. (1996). Central hypotensive effects of the α2a-adrenergic receptor subtype. Science273:801–803. [DOI] [PubMed] [Google Scholar]
  18. Madden, C. J., Ito, S., Rinaman, L., Wiley, R. G., and Sved, A. F. (1999). Lesions of the C1 catecholaminergic neurons of the ventrolateral medulla in rats using anti-DβH-saporin. Am. J. Physiol. 277(4):R1063-R1075. [DOI] [PubMed] [Google Scholar]
  19. McAllen, R. M. (1986). Identification and properties of sub-retrofacial bulbospinal neurons: A descending cardiovascular pathway in the cat. J. Auton. Nerv. Syst. 17:151–164. [DOI] [PubMed] [Google Scholar]
  20. McAllen, R. M., Habler, H. J., Michaelis, M., Peters, O., and Jäning, W. (1994). Monosynaptic excitation of preganglionic vasomotor neurons by subretrofacial neurons of the rostral ventrolateral medulla. Brain Res. 634:227–234. [DOI] [PubMed] [Google Scholar]
  21. Milner, T. A., Morrison, S. F., Abate, C., and Reis, D. J. (1988). Phenylethanolamine N-methyltransferase-containing terminals synapse directly on sympathetic preganglionic neurons in the rat. Brain Res. 448:205–222. [DOI] [PubMed] [Google Scholar]
  22. Milner, T. A., Pickel, V. M., Park, D. H., Joh, T. H., and Reis, D. J. (1987). Phenylethanolamine N-methyltransferase-containing neurons in the rostral ventrolateral medulla of the rat. I. Normal ultrastructure. Brain Res. 411:28–45. [DOI] [PubMed] [Google Scholar]
  23. Miura, M., Takayama, K., and Okada, J., (1994). Distribution of glutamate-and GABA-immunoreactivity neurons projecting to the cardioacceleratory center of the intermediolateral nucleus of the thoracic cord of SHR and WKY rats: A double labeling studio. Brain Res. 638:139–150. [DOI] [PubMed] [Google Scholar]
  24. Oshima, N., Kumagai, H., Kawai, A., Sakata, M. K., Matsuura, T., and Saruta, T. (2000). Three types of putative presympathetic neurons in the rostral ventrolateral medulla studied with rat brainstem-spinal cord preparation Auton. Neurosci. 84:40–49. [DOI] [PubMed] [Google Scholar]
  25. Paxinos, G., and Watson, C. (1986). The Rat Brain in Stereotaxic Coordinates, 2nd edn. Academic Press, New York. [Google Scholar]
  26. Privitera, P. J., Granata, A. R., Underwood, M., Gaffney, T. E., and Reis D. J. (1988). C1 area of the rostral ventrolateral medulla as a site for the central hypotensive action of propranolol. J. Pharmacol. Exp. Ther. 246(2) 529–533. [PubMed] [Google Scholar]
  27. Ross, C. A., Ruggiero, D. A., Joh, T. H., Park, D. H., and Reis, D. J. (1984). Rostral ventrolateral medulla: Selective projections to the thoracic autonomic cell column from the region containing C1 adrenergic neurons J. Comp. Neurol. 228:168–185. [DOI] [PubMed] [Google Scholar]
  28. Ross, C. A., Ruggiero, D. A., Park, D. H., Joh, T. H., Sved, A. F., Fernandez-Pardal, J., Saavedra, J. M., and Reis, D. J. (1984). Tonic vasomotor control by the rostral ventrolateral medulla: Effect of electrical and chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, plasma catecholamines and vasopressin. J. Neurosci. 4:474–494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ruggiero, D. A., Meeley, M. P., Anwar, M., and Reis, D. J. (1985). Newly identified GABAergic neurons in regions of the ventrolateral medulla which regulate blood pressure. Brain Res. 339:171–177. [DOI] [PubMed] [Google Scholar]
  30. Schreihofer, A. M., and Guyenet, P. G. (2000). Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats. Am. J. Physiol. 279:R1753-R1762. [DOI] [PubMed] [Google Scholar]
  31. Sun, M. K. (1995). Central neural organization and control of sympathetic nervous system in mammals. Prog. Neurobiol. 47:157–233. [DOI] [PubMed] [Google Scholar]
  32. Sun, M. K. (1996). Pharmacology of reticulospinal vasomotor neurons in cardiovascular regulation. Pharmacol. Rev. 48:465–494. [PubMed] [Google Scholar]
  33. Sun, M. K., and Guyenet, P. G. (1990). Excitation of rostral medullary pacemaker neurons with putative sympathoexcitatory function by cyclic AMP and α-adrenoceptor agonists “in vitro.” Brain Res. 511:30–40. [DOI] [PubMed] [Google Scholar]
  34. Sun, M. K., Hackett, J. T., and Guyenet, P. G. (1988). Sympathoexcitatory neurons of rostral ventrolateral medulla exhibit pacemaker properties in the presence of a glutamate-receptor antagonist. Brain Res. 438:23–40. [DOI] [PubMed] [Google Scholar]
  35. Terui, N., Saeki, Y., and Kumada, M. (1986). Barosensory neurons in the ventrolateral medulla in rabbits and their responses to various afferent inputs from peripheral and central sources. Jpn. J. Physiol. 36:1141–1164. [DOI] [PubMed] [Google Scholar]
  36. Tseng, C. J., Lin, H. C., Wang, S. D., and Tung, C. S. (1993). Immunohistochemical study of catecholamines enzymes and neuropeptide Y (NPY) in the rostral ventrolateral medulla and bulbospinal projections. J. Comp. Neurol. 334:294–303. [DOI] [PubMed] [Google Scholar]
  37. Unnerstall, J. R., Kopajtic, T. A., and Kuhar, M. J. (1984). Distribution of α2 agonist binding sites in the rat and human central nervous system: Analysis of some functional, anatomical correlates of the pharmacologic effects of clonidine and related adrenergic agents. Brain Res. 319:69–101. [DOI] [PubMed] [Google Scholar]
  38. Zagon, A., and Spyer, K. M. (1996). Stimulation of aortic nerve evokes three different response patterns in neurons of rostral VLM of the rat. Am. J. Physiol. 271:R1720-R1728. [DOI] [PubMed] [Google Scholar]

Articles from Cellular and Molecular Neurobiology are provided here courtesy of Springer

RESOURCES