Mammalian-specific OR37 receptors are differentially activated by distinct odorous fatty aldehydes.

The capacity of the mammalian olfactory system to detect an enormous collection of different chemical compounds is based on a large repertoire of odorant receptors (ORs). A small group of these ORs, the OR37 family, is unique due to a variety of special features. Members of this subfamily are exclusively found in mammals, they share a high degree of sequence homology and are highly conserved during evolution. It is still elusive which odorants may activate these atypical receptors. We have reasoned that compounds from skin, hairs, or skin glands might be potential candidates. We have exposed mice to such compounds and monitored activation of glomeruli through the expression of the activity marker c-fos in juxtaglomerular cells surrounding ventrally positioned glomeruli in the olfactory bulb (OB). Employing this methodology it was found that stimulation with long-chain alkanes elicits activation in the ventral part of the OB, however, none of the OR37 glomeruli. Analyses of long-chain hydrocarbon compounds with different functional groups revealed that long-chain aliphatic aldehydes elicited an activation of defined OR37 glomeruli, each of them responding preferentially to an aldehyde with different chain lengths. These results indicate that OR37 receptors may be tuned to distinct fatty aldehydes with a significant degree of ligand specificity.

[1]  Peter Mombaerts,et al.  Odorant Receptor Expression Defines Functional Units in the Mouse Olfactory System , 2002, The Journal of Neuroscience.

[2]  A. Brooke,et al.  Lipid compounds in secretions of fishing bat,Noctilio leporinus (Chiroptera: Noctilionidae) , 1996, Journal of Chemical Ecology.

[3]  P. Mombaerts,et al.  Characterization of a cluster comprising ∼100 odorant receptor genes in mouse , 2000, Mammalian Genome.

[4]  H. Breer,et al.  Olfactory neurones expressing distinct odorant receptor subtypes are spatially segregated in the nasal neuroepithelium , 1994, Cell and Tissue Research.

[5]  D. Lancet,et al.  Sequence analysis in the olfactory receptor gene cluster on human chromosome 17: recombinatorial events affecting receptor diversity. , 1996, Genomics.

[6]  H. Breer,et al.  Sequence analyses of the olfactory receptor gene cluster mOR37 on mouse chromosome 4. , 2000, Genomics.

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

[8]  T. Bonhoeffer,et al.  Tuning and Topography in an Odor Map on the Rat Olfactory Bulb , 2001, The Journal of Neuroscience.

[9]  B. Malnic Searching for the Ligands of Odorant Receptors , 2007, Molecular Neurobiology.

[10]  Lawrence C. Katz,et al.  Representation of Natural Stimuli in the Rodent Main Olfactory Bulb , 2006, Neuron.

[11]  Peter Mombaerts,et al.  Genes and ligands for odorant, vomeronasal and taste receptors , 2004, Nature Reviews Neuroscience.

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

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

[14]  L. C. Katz,et al.  An imaging-based approach to identify ligands for olfactory receptors , 2004, Neuropharmacology.

[15]  Hanyi Zhuang,et al.  Synergism of Accessory Factors in Functional Expression of Mammalian Odorant Receptors* , 2007, Journal of Biological Chemistry.

[16]  L. Buck,et al.  The human olfactory receptor gene family. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[17]  T. Morelli,et al.  Anogenital gland secretions of Lemur catta and Propithecus verreauxi coquereli: A preliminary chemical examination , 2004, American journal of primatology.

[18]  H Breer,et al.  Small subfamily of olfactory receptor genes: structural features, expression pattern and genomic organization. , 1999, Gene.

[19]  M. Leon,et al.  Multidimensional chemotopic responses to n‐aliphatic acid odorants in the rat olfactory bulb , 1999, The Journal of comparative neurology.

[20]  Shuichi Hirono,et al.  Topographic representation of odorant molecular features in the rat olfactory bulb. , 2004, Journal of neurophysiology.

[21]  Andreina Santagostino,et al.  A User-Friendly Entry to 2-Iodoxybenzoic Acid (IBX) , 1999 .

[22]  B. Trask,et al.  Genomic analysis of orthologous mouse and human olfactory receptor loci , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  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.

[24]  Richard Axel,et al.  Topographic organization of sensory projections to the olfactory bulb , 1994, Cell.

[25]  Y. Yoshihara,et al.  Odorant Receptor Map in the Mouse Olfactory Bulb: In Vivo Sensitivity and Specificity of Receptor-Defined Glomeruli , 2006, Neuron.

[26]  S. Shuster,et al.  Control and function of sebaceous glands. , 1989, Physiological reviews.

[27]  L. Buck,et al.  The mouse olfactory receptor gene family , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Lixing Sun,et al.  Sex- and Gonad-Affecting Scent Compounds and 3 Male Pheromones in the Rat , 2008, Chemical senses.

[29]  Fahmeed Hyder,et al.  Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Matt Wachowiak,et al.  Correspondence between odorant-evoked patterns of receptor neuron input and intrinsic optical signals in the mouse olfactory bulb. , 2003, Journal of neurophysiology.

[31]  B. Trask,et al.  The sense of smell: genomics of vertebrate odorant receptors. , 2002, Human molecular genetics.

[32]  Michael Leon,et al.  Local and global chemotopic organization: General features of the glomerular representations of aliphatic odorants differing in carbon number , 2004, The Journal of comparative neurology.

[33]  M. Frigerio,et al.  A mild oxidizing reagent for alcohols and 1,2-diols: o-iodoxybenzoic acid (IBX) in DMSO , 1994 .

[34]  A. Grinvald,et al.  Spatio-Temporal Dynamics of Odor Representations in the Mammalian Olfactory Bulb , 2002, Neuron.

[35]  Linda B. Buck,et al.  A zonal organization of odorant receptor gene expression in the olfactory epithelium , 1993, Cell.

[36]  Michael Leon,et al.  Long hydrocarbon chains serve as unique molecular features recognized by ventral glomeruli of the rat olfactory bulb , 2006, The Journal of comparative neurology.

[37]  Linda B. Buck,et al.  Information coding in the olfactory system: Evidence for a stereotyped and highly organized epitope map in the olfactory bulb , 1994, Cell.

[38]  M. Wachowiak,et al.  Imaging Odor Coding and Synaptic Plasticity in the Mammalian Brain with a Genetically-Encoded Probe , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[39]  H. Breer,et al.  Organization and evolutionary relatedness of OR37 olfactory receptor genes in mouse and human. , 2003, Genomics.

[40]  L. Buck,et al.  Combinatorial Receptor Codes for Odors , 1999, Cell.

[41]  Dietmar Krautwurst,et al.  The human TAS2R16 receptor mediates bitter taste in response to β-glucopyranosides , 2002, Nature Genetics.

[42]  D. Restrepo,et al.  Sensory‐dependent asymmetry for a urine‐responsive olfactory bulb glomerulus , 2008, The Journal of comparative neurology.

[43]  Fumiaki Imamura,et al.  Optical imaging of postsynaptic odor representation in the glomerular layer of the mouse olfactory bulb. , 2009, Journal of neurophysiology.

[44]  C. Gall,et al.  Odor-induced increases in c-fos mRNA expression reveal an anatomical "unit" for odor processing in olfactory bulb. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Yoshihiro Yoshihara,et al.  Molecular recognition and olfactory processing in the mammalian olfactory system , 1995, Progress in Neurobiology.

[46]  H. Breer,et al.  Subfamily of Olfactory Receptors Characterized by Unique Structural Features and Expression Patterns , 1997, Journal of neurochemistry.

[47]  Richard Axel,et al.  Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium , 1993, Cell.

[48]  K. Touhara Deorphanizing vertebrate olfactory receptors: Recent advances in odorant-response assays , 2007, Neurochemistry International.

[49]  Michael Leon,et al.  Functional mapping of the rat olfactory bulb using diverse odorants reveals modular responses to functional groups and hydrocarbon structural features , 2002, The Journal of comparative neurology.

[50]  R. Araneda,et al.  The molecular receptive range of an odorant receptor , 2000, Nature Neuroscience.

[51]  P. Duchamp-Viret,et al.  Odor response properties of rat olfactory receptor neurons. , 1999, Science.

[52]  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.

[53]  W. F. Wood Volatile Components in Metatarsal Glands of Sika Deer, Cervus nippon , 2003, Journal of Chemical Ecology.

[54]  M. Tonoike,et al.  Tuning specificities to aliphatic odorants in mouse olfactory receptor neurons and their local distribution. , 1994, Journal of neurophysiology.

[55]  S. Korsching,et al.  Selective imaging of presynaptic activity in the mouse olfactory bulb shows concentration and structure dependence of odor responses in identified glomeruli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[56]  D. Ledbetter,et al.  Olfactory receptor gene cluster on human chromosome 17: possible duplication of an ancestral receptor repertoire. , 1994, Human molecular genetics.

[57]  H Breer,et al.  Local Permutations in the Glomerular Array of the Mouse Olfactory Bulb , 2000, The Journal of Neuroscience.

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

[59]  Michael Leon,et al.  Spatial coding of odorant features in the glomerular layer of the rat olfactory bulb , 1998 .

[60]  Chunbo Zhang,et al.  Analysis of training-induced changes in ethyl acetate odor maps using a new computational tool to map the glomerular layer of the olfactory bulb. , 2005, Chemical senses.

[61]  D. Lancet,et al.  The genomic structure of human olfactory receptor genes. , 2000, Genomics.

[62]  D. Locke,et al.  Warning Odor of the North American Porcupine(Erethizon dorsatum) , 1997, Journal of Chemical Ecology.

[63]  Kei M. Igarashi,et al.  Spatial representation of hydrocarbon odorants in the ventrolateral zones of the rat olfactory bulb. , 2005, Journal of neurophysiology.

[64]  H. Breer,et al.  Evolution of the “OR37” Subfamily of Olfactory Receptors: A Cross-Species Comparison , 2006, Journal of Molecular Evolution.

[65]  R. Apfelbach,et al.  Odor detection and odor discrimination in subadult and adult rats for two enantiomeric odorants supported by c-fos data , 2010, Behavioural Brain Research.