HYPOTHESIS AND THEORY ARTICLE published: 06 December 2011 doi: 10.3389/fnins.2011.00132 On the number of preganglionic neurons driving human postganglionic sympathetic neurons: a comparison of modeling and empirical data Vaughan G. Maceﬁeld 1,2* 1 School of Medicine, University of Western Sydney, Penrith, NSW, Australia 2 Neuroscience Research Australia, Sydney, NSW, Australia Edited by: Stuart Mazzone, University of Queensland, Australia Reviewed by: Elisabeth Lambert, Baker IDI Heart and Diabetes Institute, Australia Anthony (Tony) E. Pickering, University of Bristol, UK J. Kevin Shoemaker, The University of Western Ontario, Canada *Correspondence: Vaughan G. Maceﬁeld, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia. e-mail: v.maceﬁeld@uws.edu.au Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor, or sudomotor neurons, dis- charge with a low ﬁring probability (∼30%), generate low ﬁring rates (∼0.5 Hz) and typically ﬁre only once per cardiac interval. The purpose of the present study was to use modeling of spike trains in an attempt to deﬁne the number of preganglionic neurons that drive an individual postganglionic neuron. Artiﬁcial spike trains were generated in 1–3 preganglionic neurons converging onto a single postganglionic neuron. Each preganglionic input ﬁred with a mean interval distribution of either 1000, 1500, 2000, 2500, or 3000 ms and the SD varied between 0.5×, 1.0×, and 2.0× the mean interval; the discharge frequency of each preganglionic neuron exhibited positive skewness and kurtosis. Of the 45 patterns exam- ined, the mean discharge properties of the postganglionic neuron could only be explained by it being driven by, on average, two preganglionic neurons ﬁring with a mean interspike interval of 2500 ms and SD of 5000 ms. The mean ﬁring rate resulting from this pattern was 0.22 Hz, comparable to that of spontaneously active muscle vasoconstrictor neurons in healthy subjects (0.40 Hz). Likewise, the distribution of the number of spikes per cardiac interval was similar between the modeled and actual data: 0 spikes (69.5 vs 66.6%), 1 spike (25.6 vs 21.2%), 2 spikes (4.3 vs 6.4%), 3 spikes (0.5 vs 1.7%), and 4 spikes (0.1 vs 0.7%). Although some features of the ﬁring patterns could be explained by the postgan- glionic neuron being driven by a single preganglionic neuron, none of the emulated ﬁring patterns generated by the ﬁring of three preganglionic neurons matched the discharge of the real neurons. These modeling data indicate that, on average, human postganglionic sympathetic neurons are driven by two preganglionic inputs. Keywords: sympathetic nervous system, human, preganglionic neuron, postganglionic neuron, single-unit, microneurography INTRODUCTION et al., 2007), individual neurons still tend to ﬁre only once per Microelectrode recordings from peripheral nerves of awake cardiac interval. human subjects have revealed common features in their discharge Why is this so? We know that postganglionic neurons can ﬁre patterns of individual postganglionic sympathetic axons, includ- multiple times in a sympathetic burst, though usually no more ing a probabilistic ﬁring pattern, a tendency to ﬁre only one than four spikes per cardiac interval, and have observed that there spike per cardiac interval, an exponential distribution of instan- is a shift toward fewer solitary spikes and more multiple ﬁring in taneous frequencies, and low mean ﬁring rate (∼0.5 Hz). These obstructive sleep apnea (Elam et al., 2002), chronic obstructive features are shared across the unit types that have so far been stud- pulmonary disease (Ashley et al., 2010), panic disorder (Lam- ied: muscle vasoconstrictor (Maceﬁeld et al., 1994; Maceﬁeld and bert et al., 2006), and hyperhidrosis (Maceﬁeld et al., 2008), but Wallin, 1999a), cutaneous vasoconstrictor (Maceﬁeld and Wallin, the biggest shift was observed during the ectopic beats associated 1999b), and sudomotor (Maceﬁeld and Wallin, 1996) neurons in with heart failure (Elam and Maceﬁeld, 2001). We have argued healthy subjects (for review see Maceﬁeld et al., 2002). Moreover, previously, based on a comparison of the ﬁring properties of post- although the ﬁring probability and mean ﬁring rates of muscle ganglionic sympathetic neurons and alpha motoneurons, that the vasoconstrictor neurons have been shown to be elevated in var- duration of a sympathetic burst would limit the number of times a ious pathophysiological states, including congestive heart failure neuron can ﬁre (Maceﬁeld and Elam, 2004), but we cannot escape (Maceﬁeld et al., 1999; Elam and Maceﬁeld, 2001), obstructive the fact that the ﬁring pattern is determined by the level of synaptic sleep apnea (Elam et al., 2002), chronic obstructive pulmonary drive a given postganglionic neuron receives. disease (Ashley et al., 2010), essential hypertension (Schlaich et al., McLachlan et al. (1997) have shown that approximately one- 2004), panic disorder (Lambert et al., 2006), and obesity (Lambert third of postganglionic neurons in the superior cervical ganglion www.frontiersin.org December 2011 | Volume 5 | Article 132 | 1