The extremely broad odorant response profile of mouse olfactory sensory neurons expressing the odorant receptor MOR256‐17 includes trace amine‐associated receptor ligands

The mouse olfactory system employs ~1100 G‐protein‐coupled odorant receptors (ORs). Each mature olfactory sensory neuron (OSN) is thought to express just one OR gene, and the expressed OR determines the odorant response properties of the OSN. The broadest odorant response profile thus far demonstrated in native mouse OSNs is for OSNs that express the OR gene SR1 (also known as Olfr124 and MOR256‐3). Here we showed that the odorant responsiveness of native mouse OSNs expressing the OR gene MOR256‐17 (also known as Olfr15 and OR3) is even broader than that of OSNs expressing SR1. We investigated the electrophysiological properties of green fluorescent protein (GFP)+ OSNs in a MOR256‐17‐IRES‐tauGFP gene‐targeted mouse strain, in parallel with GFP+ OSNs in the SR1‐IRES‐tauGFP gene‐targeted mouse strain that we previously reported. Of 35 single chemical compounds belonging to distinct structural classes, MOR256‐17+ OSNs responded to 31 chemicals, compared with 10 for SR1+ OSNs. The 10 compounds that activated SR1+ OSNs also activated MOR256‐17+ OSNs. Interestingly, MOR256‐17+ OSNs were activated by three amines (cyclohexylamine, isopenthylamine, and phenylethylamine) that are typically viewed as ligands for chemosensory neurons in the main olfactory epithelium that express trace amine‐associated receptor genes, a family of 15 genes encoding G‐protein‐coupled receptors unrelated in sequence to ORs. We did not observe differences in membrane properties, indicating that the differences in odorant response profiles between the two OSN populations were due to the expressed OR. MOR256‐17+ OSNs appear to be at one extreme of odorant responsiveness among populations of OSNs expressing distinct OR genes in the mouse.

[1]  Gordon M Shepherd,et al.  Electrophysiological characterization of rat and mouse olfactory receptor neurons from an intact epithelial preparation , 1999, Journal of Neuroscience Methods.

[2]  H. Breer,et al.  Odorant receptor proteins in olfactory axons and in cells of the cribriform mesenchyme may contribute to fasciculation and sorting of nerve fibers , 2006, Cell and Tissue Research.

[3]  K. Adipietro,et al.  Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism , 2015, Proceedings of the National Academy of Sciences.

[4]  H. Breer,et al.  Expression of olfactory receptors in the cribriform mesenchyme during prenatal development. , 2004, Gene expression patterns : GEP.

[5]  N. Meunier,et al.  Postnatal Odorant Exposure Induces Peripheral Olfactory Plasticity at the Cellular Level , 2014, The Journal of Neuroscience.

[6]  Jérôme Golebiowski,et al.  Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors. , 2015, Journal of the American Chemical Society.

[7]  A. Dewan,et al.  Non-redundant coding of aversive odours in the main olfactory pathway , 2013, Nature.

[8]  Adam Dewan,et al.  An olfactory subsystem that mediates high-sensitivity detection of volatile amines. , 2012, Cell reports.

[9]  S. Firestein,et al.  The olfactory receptor gene superfamily of the mouse , 2002, Nature Neuroscience.

[10]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[11]  Linda B. Buck,et al.  A Large-Scale Analysis of Odor Coding in the Olfactory Epithelium , 2011, The Journal of Neuroscience.

[12]  X. Grosmaitre,et al.  Perforated Patch-clamp Recording of Mouse Olfactory Sensory Neurons in Intact Neuroepithelium: Functional Analysis of Neurons Expressing an Identified Odorant Receptor. , 2015, Journal of visualized experiments : JoVE.

[13]  Richard Axel,et al.  Visualizing an Olfactory Sensory Map , 1996, Cell.

[14]  J. Mainland,et al.  Odor Coding by a Mammalian Receptor Repertoire , 2009, Science Signaling.

[15]  H. Vogel,et al.  Recombinant expression and functional characterization of mouse olfactory receptor mOR256-17 in mammalian cells. , 2011, Biochemistry.

[16]  H. Breer,et al.  Differential reaction of outgrowing olfactory neurites monitored in explant culture , 2008, The Journal of comparative neurology.

[17]  X. Grosmaitre,et al.  Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice. , 2009, Chemical senses.

[18]  Alan Gelperin,et al.  Biomimetic chemical sensors using nanoelectronic readout of olfactory receptor proteins. , 2011, ACS nano.

[19]  Gordon M Shepherd,et al.  Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: a patch clamp analysis in gene-targeted mice. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Rosemary C Challis,et al.  An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors , 2015, Current Biology.

[21]  Peter Mombaerts,et al.  A Novel Multigene Family May Encode Odorant Receptors : A Molecular Basis for Odor Recognition , 2014 .

[22]  Linda B. Buck,et al.  A second class of chemosensory receptors in the olfactory epithelium , 2006, Nature.

[23]  P. Mombaerts,et al.  Local and cis Effects of the H Element on Expression of Odorant Receptor Genes in Mouse , 2007, Cell.

[24]  P. Mombaerts,et al.  Odorant responsiveness of embryonic mouse olfactory sensory neurons expressing the odorant receptors S1 or MOR23 , 2013, The European journal of neuroscience.

[25]  P. Mombaerts,et al.  Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb , 2015, The Journal of comparative neurology.

[26]  H. Breer,et al.  Olfactory Receptor Proteins in Axonal Processes of Chemosensory Neurons , 2004, The Journal of Neuroscience.

[27]  Thomas Bozza,et al.  Ultrasensitive Detection of Amines by a Trace Amine-Associated Receptor , 2013, The Journal of Neuroscience.

[28]  S. Heinemann,et al.  Spatial pattern of receptor expression in the olfactory epithelium. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Mombaerts,et al.  SR1, a Mouse Odorant Receptor with an Unusually Broad Response Profile , 2009, The Journal of Neuroscience.

[30]  Minghong Ma,et al.  Spontaneous and sensory-evoked activity in mouse olfactory sensory neurons with defined odorant receptors. , 2013, Journal of neurophysiology.

[31]  H. Breer,et al.  Adiponectin Enhances the Responsiveness of the Olfactory System , 2013, PloS one.

[32]  Adam Dewan,et al.  Uncoupling stimulus specificity and glomerular position in the mouse olfactory system , 2012, Molecular and Cellular Neuroscience.

[33]  H. Breer,et al.  Formation and maturation of olfactory cilia monitored by odorant receptor-specific antibodies , 2005, Histochemistry and Cell Biology.

[34]  Rafi Haddad,et al.  A broadly tuned mouse odorant receptor that detects nitrotoluenes , 2012, Journal of neurochemistry.

[35]  P. Mombaerts,et al.  The β2-adrenergic receptor as a surrogate odorant receptor in mouse olfactory sensory neurons , 2014, Molecular and Cellular Neuroscience.