On the Number of Preganglionic Neurons Driving Human Postganglionic Sympathetic Neurons: A Comparison of Modeling and Empirical Data

Abstract

Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor, or sudomotor neurons, discharge 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 examined, 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 postganglionic 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.

HCN hyperpolarization-activated cation channels strengthen virtual nicotinic EPSPs and thereby elevate synaptic amplification in rat sympathetic neurons

“…6A). These observations recapitulate aspects of intracellular recordings from vasoconstrictor neurons in anesthetized rats (Bratton et al 2010) and extracellular single-unit recordings from awake, healthy human subjects (Macefield 2011). Indeed, changes in vasoconstrictor sympathetic activity are often characterized in the human microneurography literature in terms of the proportion of cardiac cycles where spikes are generated.…”

“…We therefore analyzed our data to determine the effect of I h blockade and to compare it with human data from 33 vasoconstrictor neurons [see Fig. 3F in Macefield (2011)]. Each of the 7 cells used to measure synaptic gain had been stimulated with 40 s templates containing 200 cardiac cycles.…”

Physiological and pathophysiological firing properties of single postganglionic sympathetic neurons in humans

“…However, it may simply be an emergent property of the way in which postganglionic sympathetic neurons are driven. A recent modeling study supports this possibility (Macefield 2011). Model spike trains were generated by one-, two-, or three-model preganglionic neurons, with each model neuron converging onto a single postganglionic neuron, as represented schematically in Fig.…”

“…The bottom trace shows the emulated nerve recording, in which spikes are superimposed on an underlying background noise. The mean interspike interval for each preganglionic neuron was 2,500 Ϯ 5,000 (SD) ms. Reproduced from Macefield (2011). Mean data on the percentage of cardiac intervals in which units were silent (0 spikes) or generated 1, 2, 3, or 4 spikes, firing probability, and mean firing rate.…”

“…Data obtained from real muscle vasoconstrictor neurons are shown in the bottom row (data pooled from Macefield et al, 1994;Macefield and Wallin 1999b). Modified from Macefield (2011). ISI, interspike interval.…”