Grueneberg Ganglion Neurons Are Finely Tuned Cold Sensors

The Grueneberg ganglion is a newly appreciated nasal subsystem with neural connections to the olfactory forebrain, but its functional role has not been well defined. Here, weassess whether Grueneberg ganglion neurons (GGNs) function as thermosensors. By investigating the effect of acute temperature changes on the cytosolic Ca2+ concentration of genetically labeled mouse GGNs (either gender), we demonstrate that GGNs are thermosensory neurons specialized to detect a temperature decline within a given temperature window. Furthermore, GGNs comprise a relatively homogeneous cell population with respect to temperature sensitivity. GGNs do not respond to ligands of the temperature-sensitive TRP channels TRPM8 and TRPA1, suggesting a novel mechanism for temperature sensing. One possibility is a cGMP-mediated mechanism, as GGNs express the receptor guanylyl cyclase GC-G, the cGMP-sensitive phosphodiesterase PDE2 and the cGMP-sensitive channel CNGA3. Surprisingly, Cnga3-null mice show normal cooling-induced Ca2+ responses although cGMP-dependent Ca2+ increases are absent in these mice. Rather, the cooling-induced Ca2+ response of GGNs depends critically on the activity of a tetrodotoxin-sensitive voltage-gated sodium channel whereas the cGMP-dependent Ca2+ signal does not. These findings establish the Grueneberg ganglion as a sensory organ mediating cold-evoked neural responses, possibly in conjunction with the sensing of other stress-or fear-related chemical social cues.