Abstract
To directly investigate whether a monosynaptic connection exists between neurons in the rostral ventrolateral medulla (RVLM) and sympathetic preganglionic neurons (SPNs), we used simultaneous extracellular recordings of RVLM neurons and whole-cell patch-clamp recordings of SPNs at the Th2 level and analyzed them by spike-triggered averaging. We averaged 200 sweeps of membrane potentials in SPN triggered by the spikes in the RVLM neuron. No clear postsynaptic potentials were detected in the averaged wave of SPNs before angiotensin II (Ang II) superfusion, whereas during superfusion with Ang II (6 μmol/L) on the medulla oblongata side alone excitatory postsynaptic potentials (EPSPs) were clearly found in the SPN of 3 out of 10 pairs at 40±1 ms after the averaged triggering spike in the RVLM neuron. We consider them to be monosynaptic EPSPs, because 1) the averaged EPSPs exhibited a sharp rise time, 2) the onset latency of the averaged EPSPs in the SPNs after the trigger spike in the RVLM was the same as the latency of the antidromic action potentials in the RVLM neurons in response to electrical stimulation of the SPNs, and 3) the amplitude of the averaged EPSPs was over 2 mV. In summary, combining simultaneous recording and spike-triggered averaging allowed us to demonstrate a monosynaptic excitatory connection between a single RVLM neuron and a single SPN in the thoracic spinal cord. Such connections provide the basis for the maintenance of sympathetic tone and the integrative reflex that relays through the RVLM. The results explain the mechanism by which Ang II in the RVLM area increases peripheral sympathetic activity and blood pressure.
Similar content being viewed by others
Article PDF
References
Kangrga IM, Loewy AD : Whole-cell recording from visualized C1 adrenergic bulbospinal neurons: ionic mechanisms underlying vasomotor tone. Brain Res 1995; 670: 215–232.
Li YW, Bayliss DA, Guyenet PG : C1 neurons of neonatal rats: intrinsic beating properties and α2-adrenergic receptors. Am J Physiol 1995; 269: R1356–R1369.
Li Y -W, Guyenet PG : Angiotensin II decreases a resting K+ conductance in rat bulbospinal neurons of the C1 area. Circ Res 1996; 78: 274–282.
Lipski J, Kanjhan R, Kruszewska B, Rong W : Properties of presympathetic neurons in the rostral ventrolateral medulla in the rat: an intracellular study ‘in vivo.’ J Physiol 1996; 490: 729–749.
Pilowsky PM, Goodchild AK : Baroreceptor reflex pathways and neurotransmitters: 10 years on. J Hypertens 2002; 20: 1675–1688.
Dembowsky K, Czachurski J, Seller H : Three types of sympathetic preganglionic neurons with different electrophysiological properties are identified by intracellular recordings in the cat. Pflügers Arch 1986; 460: 112–120.
Bernstein-Goral H, Bohn MC : Phenylethanolamine N-methyltransferase–immunoreactive terminals synapse on adrenal preganglionic neurons in the rat spinal cord. Neuroscience 1989; 32: 521–537.
Cabot J : Sympathetic preganglionic neurons: cytoarchitecture, ultrastructure and biophysical properties, in Loewy AD, Spyer KM, (eds): Central Regulation of Autonomic Functions. New York and London, Oxford University Press, 1990, pp 44–68.
Miyawaki T, Minson J, Arnolda L, Llewellyn-Smith I, Chalmers J, Pilowsky P : AMPA/kainate receptors mediate sympathetic chemoreceptor reflex in the rostral ventrolateral medulla. Brain Res 1996; 726: 64–68.
Schreihofer AM, Guyenet PG : Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats. Am J Physiol Regul Integr Comp Physiol 2000; 27: R1753–R1762.
Pilowsky PM, Llewellyn-Smith IJ, Arnolda L, Inson J, Chalmers J : Intracellular recording from sympathetic preganglionic neurons in cat lumbar spinal cord. Brain Res 1994; 656: 319–328.
Pilowsky PM : Good vibrations? Respiratory rhythms in the central control of blood pressure. Clin Exp Pharmacol Physiol 1995; 22: 594–604.
Oshima N, Kumagai H, Kawai A, Sakata K, Matsuura T, Saruta T : Three types of putative presympathetic neurons in the rostral ventrolateral medulla studied with rat brainstem–spinal cord preparation. Auton Neurosci 2000; 84: 40–49.
Onimaru H, Homma I, Iwatsuki K : Excitation of inspiratory neurons by preinspiratory neurons in rat medulla in vitro. Brain Res Bull 1992; 29: 879–882.
Oshima N, McMullan S, Goodchild AK, Pilowsky PM : A monosynaptic connection between baroinhibited neurons in the RVLM and IML in Sprague-Dawley rats. Brain Res 2006; 1089: 153–161.
Matsuura T, Kumagai H, Kawai A, et al: Rostral ventrolateral medulla neurons of neonatal Wistar-Kyoto and spontaneously hypertensive rats. Hypertension 2002; 40: 560–565.
Matsuura T, Kumagai H, Onimaru H, et al: Electrophysiological properties of rostral ventrolateral medulla neurons in angiotensin II 1a receptor knockout mice. Hypertension 2005; 46: 349–354.
Ezure K, Manabe M : Decrementing expiratory neurons of the Boezinger complex. Exp Brain Res 1988; 72: 159–166.
Iwamoto Y, Sasaki S : Monosynaptic excitatory connection of reticulospinal neurones in the nucleus reticularis pontis caudalis with dorsal neck motoneurons in the cat. Exp Brain Res 1990; 80: 277–289.
Jiang C, Lipski J : Extensive monosynaptic inhibition of ventral respiratory group neurones by augmenting neurons in the Botzinger complex in the cat. Exp Brain Res 1990; 81: 639–648.
Lipski J, Kubin L, Jodkowski J : Synaptic action of Rβ neurons on phrenic motoneurons studied with spike-triggered averaging. Brain Res 1983; 288: 105–118.
Ono K, Shiba K, Nakazawa K, Shimoyama I : Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons. Neuroscience 2006; 140: 1079–1088.
Deuchars SA, Morrison SF, Gilbey MP : Medually-evoked EPSPs in neonatal rat sympathetic preganglionic neurons in vitro. J Physiol 1995; 487: 453–463.
Lipski J : Antidromic activation of neurons as an analytical tool in the study of the central nervous system. J Neurosci Methods 1981; 4: 1–32.
Grimwood PD, Appenteng K, Curtis JC : Monosynaptic EPSPs elicited by single interneurones and spindle afferents in trigeminal motoneurones of anaesthetized rats. J Physiol 1992; 455: 641–662.
Jack JB, Miller S, Porter R, Redman SJ : The time course of minimal excitatory post-synaptic potentials evoked in spinal motoneurones by group Ia afferent fibres. J Physiol 1971; 215: 353–380.
Mendell LM, Henneman E : Terminal of single Ia fibers: location, density and distribution within a pool of 300 homonymous motoneurons. J Physiol 1971; 356: 79–113.
Barman SM, Gebber GL : Rostral ventrolateral medullary and caudal medullary raphe neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge. J Neurophysiol 1992; 68: 1535–1547.
McAllen RM, Habler HJ, Michaelis M, Peters O, Janig W : Monosynaptic excitation of preganglionic vasomotor neurons by subretrofacial neurons of the rostral ventrolateral medulla. Brain Res 1994; 634: 227–234.
Barman SM, Gebber GL : Subgroups of rostral ventrolateral medullary and caudal medullary raphe neurons based on patterns of relationship to sympathetic nerve discharge and axonal projections. J Neurophysiol 1997; 77: 65–75.
Jackson VM, Trout SJ, Brain KL, Cunnane TC : Characterization of action potential-evoked calcium transients in mouse postganglionic sympathetic axon bundles. J Physiol 2001; 537: 3–16.
Brain KL, Jackson VM, Trout SJ, Cunnane TC : Intermittent ATP release from nerve terminals elicits focal smooth muscle Ca2+ transients in mouse vas deferens. J Physiol 2002; 541: 849–862.
Hu L, Zhu D -N, Yu Z, Wang JQ, Sun Z -J, Yao T : Expression of angiotensin II type 1 (AT1) receptor in the rostral ventrolateral medulla in rats. J Appl Physiol 2002; 92: 2153–2161.
Saigusa T, Iriki M, Arita J : Brain angiotensin II tonically modulates sympathetic baroreflex in rabbit ventrolateral medulla. Am J Physiol 1996; 271: 1015–1021.
Guyenet PG : Role of the ventral medulla oblongata in blood pressure regulation, in Loewy AD, Spyer KM (eds): Central Regulation of Autonomic Functions. New York and London, Oxford University Press, 1990, pp 145–167.
Chalmers J, Pilowsky P : Brainstem and bulbospinal neurotransmitter systems in the control of blood pressure. J Hypertens 1991; 9: 675–694.
Hayar A, Feltz P, Pignet P : Adrenergic response in silent and putative inhibitory pacemaker-like neurons of the rat rostral ventrolateral medulla in vitro. Neuroscience 1997; 77: 199–217.
Granata AR, Ruggiero DA : Evidence of disynaptic projections from the rostral ventrolateral medulla to the thoracic spinal cord. Brain Res 1998; 781: 329–334.
Strack AM, Sawyer WB, Hughes JH, Platt KB, Loewy AD : A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections. Brain Res 1989; 491: 156–162.
Polosa C, Schondorf R, Laskey W : Stabilization of the discharge rate of sympathetic preganglionic neurons. J Auton Nerv Syst 1982; 5: 45–54.
Wilson JM, Coderre E, Renaud LP, Spanswick D : Active and passive membrane properties of rat sympathetic preganglionic neurones innervating the adrenal medulla. J Physiol 2002; 545: 945–960.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Oshima, N., Kumagai, H., Onimaru, H. et al. Monosynaptic Excitatory Connection from the Rostral Ventrolateral Medulla to Sympathetic Preganglionic Neurons Revealed by Simultaneous Recordings. Hypertens Res 31, 1445–1454 (2008). https://doi.org/10.1291/hypres.31.1445
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.31.1445
Keywords
This article is cited by
-
SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats
Hypertension Research (2024)
-
Clarification of hypertension mechanisms provided by the research of central circulatory regulation
Hypertension Research (2023)
-
Central blockade of the AT1 receptor attenuates pressor effects via reduction of glutamate release and downregulation of NMDA/AMPA receptors in the rostral ventrolateral medulla of rats with stress-induced hypertension
Hypertension Research (2019)
-
An in vitro experimental model for analysis of central control of sympathetic nerve activity
The Journal of Physiological Sciences (2017)
-
Expression and functions of β1- and β2-adrenergic receptors on the bulbospinal neurons in the rostral ventrolateral medulla
Hypertension Research (2014)