Maceﬁeld Modeling human postganglionic neuronal ﬁring from single postganglionic neurons occasionally revealed instan- taneous frequencies of 400 Hz, approaching the theoretical limit of 500 Hz (Maceﬁeld et al., 1994, 2002; Maceﬁeld and Wallin, 1996, 1999a,b). The model neurons could generate frequencies that were artiﬁcially higher than this, but could also generate intermittent peak instantaneous frequencies that were similar to those recorded from real neurons. Nevertheless, the incidence of short interspike intervals (≤20 ms) was very low, typically < 2%. LIMITATIONS There were several assumptions made in this study. First, the discharge of the model preganglionic neurons was composed of randomly generated interspike intervals, whereas we know that individual muscle vasoconstrictor neurons are constrained by the arterial baroreceptors to ﬁre with a tight cardiac rhythmicity, and that even cutaneous vasoconstrictor and sudomotor neu- rons do exhibit some cardiac rhythmicity (Maceﬁeld and Wallin, 1996, 1999b). Nevertheless, like the real neurons, the distribution of ﬁring rates was exponential: it was positively skewed with a positive kurtosis (Maceﬁeld et al., 2002). In many respects, the randomly occurring spikes largely mimicked that of actual post- ganglionic neurons, the ﬁring of which appears to be probabilistic in nature. We know that the interspike intervals of neurons in the superior cervical ganglion of the anesthetized rat are exponentially distributed, that bursts of impulses occur through chance, and that cardiac and respiratory rhythms can entrain the discharge (McLachlan et al., 1998). Second, as noted above, there were no biophysical constraints as to the shortest interspike interval, but given that these were rare I don’t believe this has a major impact on the interpretation. Third, it is assumed that the presynaptic neurons are exclusively excitatory – dominated by “strong” or “pri- mary” inputs in which there is faithful synaptic security between a given preganglionic neuron and the postganglionic neuron it supplies. And fourth, the mean ﬁring rate of each of the model preganglionic neurons was equal: this is not unreasonable, but assumes that the descending excitatory drive from the medulla is distributed uniformly within the pool of preganglionic neurons in the spinal cord. CONCLUSION Not withstanding these limitations, on the basis of modeling the ﬁring properties of preganglionic neurons and comparing these with the ﬁring of real postganglionic neurons it is concluded that the ﬁring properties of single muscle vasoconstrictor neu- rons recorded in awake human subjects appear to be an emergent property of the probabilistic discharge of – on average – two preganglionic neurons converging onto the one postganglionic neuron. None of the ﬁring patterns generated by the convergence of three preganglionic neurons matched the discharge of the real postganglionic neurons. REFERENCES Ashley, C., Burton, D., Sverrisdottir, Y. B., Sander, M., McKenzie, D. K., and Maceﬁeld, V. G. (2010). Fir- ing probability and mean ﬁring rates of human muscle vasocon- strictor neurones are elevated dur- ing chronic asphyxia. J. Physiol. 588, 701–711. Bratton, B., Davies, P., Jänig, W., and McAllen, R. (2010). Ganglionic transmission in a vasomotor path- way studied in vivo. J. Physiol. 588, 1647–1659. Elam, M., and Maceﬁeld, V. G. (2001). Multiple ﬁring of single muscle vaso- constrictor neurons during cardiac dysrhythmias in human heart fail- ure. J. Appl. Physiol. 91, 717–724. Elam, M., Maceﬁeld, V. G., and McKen- zie, D. (2002). The ﬁring pattern of single muscle vasoconstrictor neu- rons in awake patients with the obstructive sleep apnoea syndrome. J. Appl. Physiol. 93, 297–303. Lambert, E., Hotchkin, E., Alvarenga, M., Pier, C., Richards, J., Barton, D., Dawood, T., Esler, M., and Lam- bert, G. (2006). Single-unit analysis of sympathetic nervous discharges in patients with panic disorder. J. Physiol. 570, 637–643. Lambert, E., Straznicky, N., Schlaich, M., Esler, M., Dawood, T., Hotchkin, E., and Lambert, G. (2007). Dif- fering pattern of sympathoexcita- tion in normal-weight and obesity- related hypertension. Hypertension 50, 862–868. Li, C., and Horn, J. P. (2006). Physiological classiﬁcation of sympathetic neurons in the rat superior cervical ganglion. J. Neurophysiol. 95, 187–195. Maceﬁeld, V. G., and Elam, M. (2004). Comparison of the ﬁring patterns of human postganglionic sympathetic neurones and spinal α motoneu- rones during brief bursts. Exp. Phys- iol. 89, 82–88. Maceﬁeld, V. G., Elam, M., and Wallin, B. G. (2002). Firing properties of sin- gle postganglionic sympathetic neu- rones recorded in awake human sub- jects. Auton. Neurosci. 95, 146–159. Maceﬁeld, V. G., Rundqvist, B., Sver- risdottir, Y. B., Wallin, B. G., and Elam, M. (1999). Firing properties of single muscle vasoconstrictor neu- rons in the sympathoexcitation asso- ciated with congestive heart failure. Circulation 100, 1708–1713. Maceﬁeld, V. G., Sverrisdottir, Y. B., Elam, E., and Harris, J. (2008). Firing properties of sudomotor neurones in hyperhidrosis and thermal sweat- ing. Clin. Auton. Res. 18, 325–330. Maceﬁeld, V. G., and Wallin, B. G. (1996). Discharge behaviour of sin- gle sympathetic neurones innervat- ing human sweat glands. J. Auton. Nerv. Syst. 61, 277–286. Maceﬁeld, V. G., and Wallin, B. G. (1999a). Firing properties of sin- gle vasoconstrictor motoneurones in subjects with high levels of muscle sympathetic activity. J. Physiol. 516, 293–301. Maceﬁeld, V. G., and Wallin, B. G. (1999b). Respiratory and cardiac modulation of single vasoconstrictor and sudomotor neurones to human skin. J. Physiol. 516, 303–314. Maceﬁeld, V. G., Wallin, B. G., and Vallbo, Å. B. (1994). The discharge behaviour of single vasoconstric- tor motoneurones in human muscle nerves. J. Physiol. 481, 799–809. McLachlan, E. M., Davies, P. J., Häbler, H. J., and Jamieson, J. (1997). On- going and reﬂex synaptic events in rat superior cervical ganglion cells. J. Physiol. 501, 165–182. McLachlan, E. M., Habler, H. J., Jamieson, J., and Davies, P. J. (1998). Analysis of the periodicity of synap- tic events in neurones in the superior cervical ganglion of anaesthetized rats. J. Physiol. (Lond.) 511, 461–478. Rimmer, K., and Horn, J. P. (2010). Weak and straddling secondary nicotinic synapses can drive ﬁr- ing in rat sympathetic neurons and thereby contribute to ganglionic ampliﬁcation. Front. Neurol. 1:130. doi:10.3389/fneur.2010.00130 Salmanpour, A., Brown, L. J., Steinback, C. D., Usselman, C. W., Goswami, R., and Shoemaker, J. K. (2011). Rela- tionship between size and latency of action potentials in human muscle sympathetic nerve activity. J. Neuro- physiol. 105, 2830–2842. Schlaich, M. P., Lambert, E., Kaye, D. M., Krozowski, Z., Campbell, D. J., Lambert, G., Hastings, J., Aggarwal, A., and Esler, M. D. (2004). Sympathetic augmentation in hypertension: role of nerve ﬁring, norepinephrine reuptake, and angiotensin neuromodulation. Hypertension 43, 169–175. Steinback, C. D., Salmanpour, A., Breskovic, T., Dujic, Z., and Shoe- maker, J. K. (2010). Sympathetic neural activation: an ordered affair. J. Physiol. (Lond.) 588, 4825–4836. Conﬂict of Interest Statement: The author declares that the research was conducted in the absence of any commercial or ﬁnancial relationships that could be construed as a potential conﬂict of interest. Received: 02 October 2011; accepted: 14 November 2011; published online: 06 December 2011. Citation: Maceﬁeld VG (2011) On the number of preganglionic neurons dri- ving human postganglionic sympathetic neurons: a comparison of modeling and empirical data. Front. Neurosci. 5:132. doi: 10.3389/fnins.2011.00132 This article was submitted to Frontiers in Autonomic Neuroscience, a specialty of Frontiers in Neuroscience. Copyright © 2011 Maceﬁeld. This is an open-access article distributed under the terms of the Creative Commons Attribu- tion Non Commercial License, which per- mits non-commercial use, distribution, and reproduction in other forums, pro- vided the original authors and source are credited. Frontiers in Neuroscience | Autonomic Neuroscience December 2011 | Volume 5 | Article 132 | 6