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Receptor guanylyl cyclase-G is a novel thermosensor in Grueneberg ganglion neurons involved in coolness-induced ultrasonic distress calls in mice

  • 1,
  • 2,
  • 1,
  • 1,
  • 2 and
  • 1, 3Email author
BMC Pharmacology and Toxicology201314 (Suppl 1) :P14

  • Published:


  • Dorsal Root Ganglion
  • Cool Temperature
  • Trigeminal Ganglion
  • TRPM8 Channel
  • Ultrasonic Vocalization


In mammals, detection of ambient temperatures is mainly mediated by thermosensory neurons residing in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) [13]. Recently, neurons in the Grueneberg ganglion (GG) of the murine nasal vestibule have been found to be activated by cool temperatures [4, 5]. Unlike coolness-sensitive cells in the DRG and TG, neurons in the GG lack the TRPM8 channel [6] which is considered as a principal detector of cold [13]. Therefore, GG neurons are supposedly endowed with a so far unknown thermosensor. Interestingly, coolness-sensitive GG neurons express signaling elements associated with cyclic guanosine monophosphate (cGMP), including the cGMP-activated ion channel CNGA3 and receptor guanylyl cyclase-G (GC-G) [68]. Recent observations suggest that cGMP signaling is crucial for thermotransduction in the GG [8]. However, whether GC-G directly acts as a temperature sensor remains elusive.

Materials and methods

A combination of biochemical and molecular biology methods, Ca2+ imaging as well as behavioural studies comparing wild-type and GC-G-knockout mice was used to elucidate the molecular and biological function of GC-G in sensing cool temperatures.


We show that GC-G is a thermosensory receptor that can be maximally stimulated by cool temperatures of about 15°C in both in vivo cellular cGMP accumulation assays and in vitro GC assays with a purified recombinant protein. Cells co-expressing GC-G and CNGA3 respond to cool temperatures via a rapid influx of calcium. Furthermore, we found a marked coolness-induced expression of the activity-dependent gene c-Fos in GG neurons of wild-type neonatal pups but not in GC-G-knockout conspecifics. Consistent with these findings, coolness-elicited ultrasonic vocalizations were significantly impaired in GC-G-knockout compared to wild-type pups.


Our data suggest that GC-G is a novel thermosensory protein and that GG activation via GC-G by coolness is critical for the generation of ultrasound calls by isolated pups to elicit maternal care.

Authors’ Affiliations

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Institute of Physiology, University of Hohenheim, Stuttgart, Germany
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan


  1. Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D: The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007, 448: 204-208. 10.1038/nature05910.View ArticlePubMedGoogle Scholar
  2. Colburn RW, Lubin ML, Stone DJ, Wang Y, Lawrence D, D'Andrea MR, Brandt M, Liu Y, Flores CM, Qin N: Attenuated cold sensitivity in TRPM8 null mice. Neuron. 2007, 54: 379-386. 10.1016/j.neuron.2007.04.017.View ArticlePubMedGoogle Scholar
  3. Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A: TRPM8 is required for cold sensation in mice. Neuron. 2007, 54: 371-378. 10.1016/j.neuron.2007.02.024.View ArticlePubMedGoogle Scholar
  4. Mamasuew K, Breer H, Fleischer J: Grueneberg ganglion neurons respond to cool ambient temperatures. Eur J Neurosci. 2008, 28: 1775-1785. 10.1111/j.1460-9568.2008.06465.x.View ArticlePubMedGoogle Scholar
  5. Schmid A, Pyrski M, Biel M, Leinders-Zufal T, Zufall F: Grueneberg ganglion neurons are finely tuned cold sensors. J Neurosci. 2010, 30: 7563-7568. 10.1523/JNEUROSCI.0608-10.2010.View ArticlePubMedGoogle Scholar
  6. Fleischer J, Mamasuew K, Breer H: Expression of cGMP signaling elements in the Grueneberg ganglion. Histochem Cell Biol. 2009, 131: 75-88. 10.1007/s00418-008-0514-8.View ArticlePubMedGoogle Scholar
  7. Liu CY, Frase SE, Koos DS: Grueneberg ganglion olfactory subsystem employs a cGMP signaling pathway. J Comp Neurol. 2009, 516: 36-48. 10.1002/cne.22096.PubMed CentralView ArticlePubMedGoogle Scholar
  8. Mamasuew K, Michalakis S, Breer H, Biel M, Fleischer J: The cyclic nucleotide-gated ion channel CNGA3 contributes to coolness-induced responses of Grueneberg ganglion neurons. Cell Mol Life Sci. 2010, 67: 1859-1869. 10.1007/s00018-010-0296-8.View ArticlePubMedGoogle Scholar


© Chao et al; licensee BioMed Central Ltd. 2013

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