Population encoding of cool and warm by thermoreceptors

Innocuous temperature sensation arises from the activity of primary afferent thermoreceptors, but how these neurons encode cool and warm at the population level remains unclear. Using two-photon in vivo imaging of the L4 dorsal root ganglion in awake and anesthetized mice, we show that the thermoreceptor population is strongly biased toward activation by cooling and suppression of activity by warming. Although thermoreceptors activated by cool or warm only are present in the population, most show bidirectional responses and encode absolute temperatures in a graded manner. Pharmacological manipulations and computational modeling suggest that both activation and suppression could arise from a single cool-selective channel, TRPM8, with diverse response profiles explained by differences in TRPM8 conductance. Our findings support a model in which innocuous temperature is largely encoded by a single functional class of thermoreceptor via graded, bidirectional changes in activity rather than exclusively by anatomically and functionally distinct cool and warm cells.