Detection of Near-Atmospheric Concentrations of CO2 by an Olfactory Subsystem in the Mouse

Carbon dioxide (CO2) is an important environmental cue for many organisms but is odorless to humans. It remains unclear whether the mammalian olfactory system can detect CO2 at concentrations around the average atmospheric level (0.038%). We demonstrated the expression of carbonic anhydrase type II (CAII), an enzyme that catabolizes CO2, in a subset of mouse olfactory neurons that express guanylyl cyclase D (GC-D+ neurons) and project axons to necklace glomeruli in the olfactory bulb. Exposure to CO2 activated these GC-D+ neurons, and exposure of a mouse to CO2 activated bulbar neurons associated with necklace glomeruli. Behavioral tests revealed CO2 detection thresholds of ∼0.066%, and this sensitive CO2 detection required CAII activity. We conclude that mice detect CO2 at near-atmospheric concentrations through the olfactory subsystem of GC-D+ neurons.

[1]  P. Avila,et al.  Real-time monitoring of nasal mucosal pH during carbon dioxide stimulation: implications for stimulus dynamics. , 2003, Chemical senses.

[2]  M. Gillies.,et al.  The Role of Carbon Dioxide in Host-Finding by Mosquitoes (Diptera: Culicidae): A Review , 1980 .

[3]  E. L. Coates,et al.  Topical inhibition of nasal carbonic anhydrase affects the CO2 detection threshold in rats. , 2007, Chemical senses.

[4]  M. Nagano,et al.  A possible functional necklace formed by placental antigen X-P2-immunoreactive and intensely acetylcholinesterase-reactive (PAX/IAE) glomerular complexes in the rat olfactory bulb , 1993, Brain Research.

[5]  R. Fernley,et al.  Carbonic Anhydrase VI in the Mouse Nasal Gland , 2004, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[6]  D. Hornung,et al.  Determination of carbon dioxide detection thresholds in trained rats , 1991, Physiology & Behavior.

[7]  J. Hildebrand,et al.  Floral CO2 Reveals Flower Profitability to Moths , 2004, Journal of Chemical Ecology.

[8]  G. Stange,et al.  Carbon‐dioxide sensing structures in terrestrial arthropods , 1999, Microscopy research and technique.

[9]  E. L. Coates.  Olfactory CO2 chemoreceptors , 2001 .

[10]  P. Pearson,et al.  Atmospheric carbon dioxide concentrations over the past 60 million years , 2000, Nature.

[11]  G M Shepherd,et al.  Functional mosaic organization of mouse olfactory receptor neurons. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Leslie B. Vosshall,et al.  Two chemosensory receptors together mediate carbon dioxide detection in Drosophila , 2007, Nature.

[13]  K. Yau,et al.  A new subunit of the cyclic nucleotide-gated cation channel in retinal rods , 1993, Nature.

[14]  D. Juilfs,et al.  A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  David J. Anderson,et al.  A single population of olfactory sensory neurons mediates an innate avoidance behaviour in Drosophila , 2004, Nature.

[16]  J. Ngai,et al.  General Anosmia Caused by a Targeted Disruption of the Mouse Olfactory Cyclic Nucleotide–Gated Cation Channel , 1996, Neuron.

[17]  Martin H. Teicher,et al.  Suckling pheromone stimulation of a modified glomerular region in the developing rat olfactory bulb revealed by the 2-deoxyglucose method , 1980, Brain Research.

[18]  B. Slotnick,et al.  Odors Detected by Mice Deficient in Cyclic Nucleotide-Gated Channel Subunit A2 Stimulate the Main Olfactory System , 2004, The Journal of Neuroscience.

[19]  E. Kremmer,et al.  A cGMP-signaling pathway in a subset of olfactory sensory neurons. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Erickson,et al.  N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[21]  W. Sly,et al.  Carbonic anhydrase gene expression in CA II‐deficient (Car2−/−) and CA IX‐deficient (Car9−/−) mice , 2006, The Journal of physiology.

[22]  Raymond E. Davis,et al.  The Ionization Constant of Carbonic Acid in Water and the Solubility of Carbon Dioxide in Water and Aqueous Salt Solutions from 0 to 50 , 1943 .

[23]  R. Axel,et al.  A receptor guanylyl cyclase expressed specifically in olfactory sensory neurons. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Restrepo,et al.  Evaluation of the validity of a maximum likelihood adaptive staircase procedure for measurement of olfactory detection threshold in mice. , 2006, Chemical senses.

[25]  R. Betts,et al.  Acceleration of global warming due to carbon-cycle feedbacks in a coupled climate model , 2000, Nature.

[26]  S. Lahiri,et al.  CO2/H(+) sensing: peripheral and central chemoreception. , 2003, The international journal of biochemistry & cell biology.

[27]  R. Khalifah,et al.  The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C. , 1971, The Journal of biological chemistry.

[28]  Burton Slotnick,et al.  Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study. , 2003, Chemical senses.