Cold sensing by Na _V 1.8-positive and Na _V 1.8-negative sensory neurons

Abstract

Significance The cellular correlate for cold sensing has been ascribed to either Trpm8-expressing or Na V 1.8-expressing neurons. Importantly, transcriptomic analysis shows that these neuronal populations are nonoverlapping. Using in vivo GCaMP imaging in live mice we show that the vast majority of acute cold-sensing neurons activated at ≥1 °C do not express Na V 1.8, and that the loss of Na V 1.8 does not affect acute cold-sensing behavior in mice. Instead, we show that cold-responding neurons are enriched with Trpm8 as well as numerous potassium channels, including Kcnk9. By contrast, Na V 1.8-positive neurons signal prolonged extreme cold. These observations highlight the complexity of cold sensing in DRG neurons, and the role of Na V 1.8-negative neurons in cold sensing down to 1 °C.