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Viewpoints |
1 School of Medicine and Medical Science, Health Science Complex, University College Dublin, Belfield, Dublin 4, Ireland
(Received 31 July 2007;
accepted after revision 16 August 2007; first published online 13 September 2007)
Corresponding author J. F. X. Jones: School of Medicine and Medical Science, Health Science Complex, University College Dublin, Belfield, Dublin 4, Ireland. Email: james.jones{at}ucd.ie
The number of vagal neurones that project to the heart is small. These cells are scattered along most of the length of the medulla and cluster ventrolaterally to the two motor nuclei of the vagus nerve, the dorsal vagal motor nucleus (DVMN) and the nucleus ambiguus (NA). There is an even smaller number of neurones dispersed in the intermediate zone between the DVMN and NA. In order to record the electrical activity of these intermediate zone rarities in the living animal, it is necessary to drive a glass electrode in a blind fashion through the medulla, locate the cells by antidromic activation of their axons near the heart and hold these neurones as they move with the pulsations transmitted by heart beat and ventilator. The cells' activities are usually depressed by anaesthesia but micro-iontophoresis of excitant amino acids evokes discharge. At the end of the experiment, the recording site must be marked. This is not an experiment for the weak of spirit, those who prefer the safety of harbour to the adventure of open sea. In this volume of Experimental Physiology we have the first paper on these rare cells by Kong et al. (2007) who, like Henry Dale, enjoy their adventures in physiology. It is necessary to explain why these experiments are worth doing, since they require hours of surgical preparation and hours of hunting and waiting for the double click of stimulus artefact and antidromic spike over the audio amplifier, often after the chimes of midnight.
The history of ideas concerning the central location of cardiac vagal preganglionic neurones (CVPNs) is instructive; it is not a waste of time to find out how others wasted theirs. Since the vagus has two motor nuclei there are three possibilities: cardiac representation may reside in the NA, the DVMN or both. After more than a century of research, there are approximately equal numbers of papers offering experimental evidence for each hypothesis. Modern advances in instrumentation and tract tracing tempt us to give more weight to recent papers, but the crucial step that led to the current and prevailing view involved a switch from retrograde to anterograde tracing. When retrograde tracers are applied to the heart, they may spill onto other thoracic organs, and this concern can never be fully ejected from the experimentalist's mind, or more pointedly a competitor's mind. However, a large and slapdash application of tracer centrally into either the DVMN or NA may label many organs but the key question arises: is label found in cardiac ganglia? The answer (in the case of the rat at least) is clearly yes (Cheng & Powley, 2000). Of interest, the NA projection to ganglia is more divergent than the DVMN projection and it is conveyed by larger diameter axons (B fibres) compared with the latter group which have C fibre axons. A consensus opinion has thus taken root that the CVPNs are located in both NA and DVMN and that the dispersion of these cells reflects a migration that occurs during fetal life from dorsal to ventral medulla. The migratory path is marked by the hairpin loops of the axons of NA vagal neurones and it is along these hairpins that the rare intermediate cells are found. These may be cells that have not migrated the full distance to the NA. The finding that the heart is represented twice in the medulla tempted some physiologists to hypothesize that the neurones in the two locations may subserve different functions. For instance, CVPNs in the NA may slow the heart but DVMN cardiac neurones may regulate the coronary arteries. A serendipitous discovery by Ford & McWilliam (1986) offered a fresh perspective. They found that both B and C fibre vagal efferents could slow the heart in the rabbit and, furthermore, the C fibre bradycardia was resistant to hexamethonium. Similar results were found for other cardiac actions of the vagus; both groups of neurones affect atrioventricular impulse conduction and vigour of contraction of the paced heart (Garcia Perez & Jordan, 2001). Thus it appears that there is both an anatomical and a functional duplication of cardiac vagal neurones in the brainstem. The purpose of such duplication remains uncertain; however, the discharge patterns for two sets of neurones in DVMN and NA are quite different. Members of the NA group display respiratory rhythm and receive baroreceptor input. The DVMN group has a more random and sparse discharge which does not have respiratory or pulse rhythm even after averaging methods are applied (Jones et al. 1998).
The paper by Kong et al. (2007), which studies the intermediate cells for the first time, provides the answer to the question: do these intermediate cells resemble the DVMN or NA group of cells? The answer is simply that intermediate cells retain the characteristics of the DVMN cells regardless of their migratory distance. I suspect that it will be a long time before this experiment is replicated, at least in the manner described by Kong et al. (2007). Perhaps a technological innovation will permit deep non-invasive recording in the future, like using a magnet to catch that needle in the haystack instead of sorting the straw by hand.
Footnotes
The author of this viewpoint and the researchers who executed this work were all trained in the technique of central recording by Professor David Jordan, whose recent death we mourn.
References
Ford TW & McWilliam PN (1986). The effects of electrical stimulation of myelinated and non-myelinated vagal fibres on heart rate in the rabbit. J Physiol 380, 341–347.
Garcia Perez M & Jordan D (2001). Effect of stimulating non-myelinated vagal axons on atrio-ventricular conduction and left ventricular function in anaesthetized rabbits. Auton Neurosci 86, 183–191.[CrossRef][Medline]
Jones JF, Wang Y & Jordan D (1998). Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats. J Physiol 507, 869–880.
Kong S, Liu J-H, Ramage AG & Wang Y (2007). Cardiac vagal preganglionic neurones in the intermediate zone of the brainstemin anaesthetized cats. Exp Physiol, DOI: 10.1113/expphysiol.2007.039230
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