Intermittent Failure of Spike Propagation in Primary Afferent Neurons during Tactile Stimulation

Primary afferent neurons convey somatosensory information to the CNS. Low-threshold mechanoreceptors 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 in vivo from DRGs of mice, we observed irregular- and regular-spiking units consistent with SA1 and SA2 low-threshold mechanoreceptors, but some units, which we labeled "semiregular," did not fit cleanly into the existing classification scheme. Analysis of their spiking revealed integer-multiple patterning in which 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 semiregular 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. Indeed, 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.