Papers of the Week

Primary afferent neurons convey somatosensory information to the central nervous system. Low-threshold mechanoreceptors (LTMRs) are classified as slow-adapting (SA) or rapid-adapting (RA) based on whether or not they spike repetitively during sustained tactile stimulation; the former are subclassified as type 1 or 2 based on the regularity of their spiking. Recording from dorsal root ganglia (DRG) of mice, we observed irregular- and regular-spiking units consistent with SA1 and SA2 LTMRs, but some units, which we labeled "semi-regular", did not fit cleanly into the existing classification scheme. Analysis of their spiking revealed integer-multiple patterning – spike trains comprised a fundamental interspike interval and multiples thereof. Integer-multiple-patterned spiking was reproduced by randomly removing spikes from an otherwise regular spike train, suggesting that semi-regular units represent SA2 units in which some spikes are "missing". We hypothesized that missing spikes arose from intermittent failure of spikes to initiate or to propagate. Intermittent failure of spike initiation was ruled out by several observations: integer-multiple-patterned spiking was not induced by intradermal lidocaine, was independent of stimulus modality (mechanical vs. optogenetic), and could not be reproduced in a conductance-based model neuron given constant input. On the other hand, integer-multiple-patterned spiking was induced by application of lidocaine to the DRG, thus pinpointing intermittent failure of spike propagation as the basis for integer-multiple-patterned spiking. In fact, half of all SA2 units exhibited some missing spikes, mostly at low rate (<5%), which suggests that axons are efficient in using the lowest safety factor capable of producing near-perfect propagation reliability.The impedance mismatch at axon branch points can impede spike propagation. Reliability of spike propagation across branch points remains an open question, and is especially important for primary afferents whose spikes must cross a T-junction in order to reach the CNS. Past research on propagation reliability has relied almost entirely on simulations and experiments. Here, recording , we linked a distinctive pattern of spiking to the intermittent failure of spike propagation at the T-junction. The rarity of failures argues that safety factor is high under physiological conditions, yet the occurrence of such failures argues that safety factor is high enough to ensure -perfect reliability, consistent with a good balance between propagation reliability and energy efficiency.