Bidirectionally responsive thermoreceptors encode cool and warm

Thermal sensation is a fundamental sense initiated by the activity of primary afferent thermoreceptors. While considerable attention has been paid to the encoding of noxious temperatures by thermoreceptors, it is far less clear how they encode innocuous cool and warm which are more commonly encountered in the environment. To address this, we sampled the entire thermoreceptor population using in vivo two-photon calcium imaging in the lumbar dorsal root ganglia of awake and anesthetized mice. We found that the vast majority of thermoreceptors respond bidirectionally, with an enhanced response to cool and a suppressed response to warm. Using in vivo pharmacology and computational modelling, we demonstrate that conductance changes in the cool-sensitive TRPM8 channel are sufficient to explain this bidirectional response type. Our comprehensive dataset reveals the fundamental principles of the peripheral encoding of innocuous temperatures and suggests that the same population of thermoreceptors underlie the distinct sensations of cool and warm.