Neural coding of binary mixtures in a structurally related odorant pair

The encoding of odorant mixtures by olfactory sensory neurons depends on molecular interactions at peripheral receptors. However, the pharmacological basis of these interactions is not well defined. Both competitive and noncompetitive mechanisms of receptor binding and activation, or suppression, could contribute to coding. We studied this by analyzing responses of olfactory bulb glomeruli evoked by a pair of structurally related odorants, eugenol (EG) and methyl isoeugenol (MIEG). Fluorescence imaging in synaptopHluorin (spH) mice revealed that EG and MIEG evoked highly overlapped glomerular inputs, increasing the likelihood of mixture interactions. Glomerular responses to binary mixtures of EG and MIEG mostly showed hypoadditive interactions at intermediate and high odorant concentrations, with a few near threshold responses showing hyperadditivity. Dose-response profiles were well fitted by a model of two odorants competitively binding and activating a shared receptor linked to a non-linear transduction cascade. We saw no evidence of non-competitive mechanisms.

[1]  DAVID G. LAING.  Coding of Chemosensory Stimulus Mixtures , 1987, Annals of the New York Academy of Sciences.

[2]  Anderson C. Lee,et al.  Olfactory Marker Protein Is Critical for Functional Maturation of Olfactory Sensory Neurons and Development of Mother Preference , 2011, The Journal of Neuroscience.

[3]  B. Ache,et al.  Inhibitory odorant signaling in Mammalian olfactory receptor neurons. , 2010, Journal of neurophysiology.

[4]  L. Cohen,et al.  Interglomerular center-surround inhibition shapes odorant-evoked input to the mouse olfactory bulb in vivo. , 2006, Journal of neurophysiology.

[5]  J. Rospars,et al.  Coding of odour intensity in a sensory neuron. , 1997, Bio Systems.

[6]  K. Touhara,et al.  An odorant derivative as an antagonist for an olfactory receptor. , 2004, Chemical senses.

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

[8]  Randall R. Reed,et al.  Identification of a specialized adenylyl cyclase that may mediate odorant detection. , 1990, Science.

[9]  C. Linster,et al.  Configurational and nonconfigurational interactions between odorants in binary mixtures. , 2003, Behavioral neuroscience.

[10]  G. Lowe,et al.  Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells , 1993, Nature.

[11]  M. Fletcher,et al.  Analytical Processing of Binary Mixture Information by Olfactory Bulb Glomeruli , 2011, PloS one.

[12]  B. Slotnick,et al.  Odor masking in the rat , 1989, Physiology & Behavior.

[13]  F. N. Jones,et al.  ON THE INTENSITY OF ODOR MIXTURES * , 1964, Annals of the New York Academy of Sciences.

[14]  S. Youngentob,et al.  Adenoviral vector-mediated rescue of the OMP-null behavioral phenotype: enhancement of odorant threshold sensitivity. , 2004, Behavioral neuroscience.

[15]  Adam C. Puche,et al.  Inhibition of Olfactory Receptor Neuron Input to Olfactory Bulb Glomeruli Mediated by Suppression of Presynaptic Calcium Influx , 2005 .

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

[17]  N. Issa,et al.  Glomerular activation patterns and the perception of odor mixtures , 2008, The European journal of neuroscience.

[18]  Leslie M Kay,et al.  A critical test of the overlap hypothesis for odor mixture perception. , 2009, Behavioral neuroscience.

[19]  Thomas A. Cleland,et al.  Concentration Tuning Mediated by Spare Receptor Capacity in Olfactory Sensory Neurons: A Theoretical Study , 1999, Neural Computation.

[20]  Michael Leon,et al.  Glomerular activity patterns evoked by natural odor objects in the rat olfactory bulb are related to patterns evoked by major odorant components , 2010, The Journal of comparative neurology.

[21]  Satoshi Hikichi,et al.  Mechanism of olfactory masking in the sensory cilia , 2009, The Journal of general physiology.

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

[23]  D. G. Laing,et al.  Quality and intensity of binary odor mixtures , 1984, Physiology & Behavior.

[24]  Leslie M Kay,et al.  A redefinition of odor mixture quality. , 2005, Behavioral neuroscience.

[25]  P. Duchamp-Viret,et al.  Interactions of odorants with olfactory receptors and receptor neurons match the perceptual dynamics observed for woody and fruity odorant mixtures , 2012, The European journal of neuroscience.

[26]  J. Rospars,et al.  Competitive and Noncompetitive Odorant Interactions in the Early Neural Coding of Odorant Mixtures , 2008, The Journal of Neuroscience.

[27]  F. Kawai.  Odorant suppression of delayed rectifier potassium current in newt olfactory receptor cells , 1999, Neuroscience Letters.

[28]  Tom Misteli,et al.  In vivo imaging. , 2003, Methods.

[29]  Matt Wachowiak,et al.  In Vivo Imaging of Neuronal Activity by Targeted Expression of a Genetically Encoded Probe in the Mouse , 2004, Neuron.

[30]  F. Kawai.  Odorants suppress T- and L-type Ca2+ currents in olfactory receptor cells by shifting their inactivation curves to a negative voltage , 1999, Neuroscience Research.

[31]  S. Itohara,et al.  Innate versus learned odour processing in the mouse olfactory bulb , 2007, Nature.

[32]  D. Restrepo,et al.  Olfactory Fingerprints for Major Histocompatibility Complex-Determined Body Odors II: Relationship among Odor Maps, Genetics, Odor Composition, and Behavior , 2002, The Journal of Neuroscience.

[33]  D. T. Jones,et al.  Golf: an olfactory neuron specific-G protein involved in odorant signal transduction. , 1989, Science.

[34]  L. Cohen,et al.  Representation of Odorants by Receptor Neuron Input to the Mouse Olfactory Bulb , 2001, Neuron.

[35]  Matt Wachowiak,et al.  Odorant Representations Are Modulated by Intra- but Not Interglomerular Presynaptic Inhibition of Olfactory Sensory Neurons , 2005, Neuron.

[36]  Shin Nagayama,et al.  Detection and Masking of Spoiled Food Smells by Odor Maps in the Olfactory Bulb , 2004, The Journal of Neuroscience.

[37]  B. Ache,et al.  Phosphoinositide 3-Kinase-Dependent Antagonism in Mammalian Olfactory Receptor Neurons , 2011, The Journal of Neuroscience.

[38]  K. Yau,et al.  Olfactory marker protein modulates the cAMP kinetics of the odour‐induced response in cilia of mouse olfactory receptor neurons , 2007, The Journal of physiology.

[39]  William S Cain,et al.  Quantification of chemical vapors in chemosensory research. , 2003, Chemical senses.

[40]  Loïc Briand,et al.  Comparison of odorant specificity of two human olfactory receptors from different phylogenetic classes and evidence for antagonism. , 2005, Chemical senses.

[41]  Thomas A. Cleland,et al.  Configurational and Elemental Odor Mixture Perception Can Arise from Local Inhibition , 2004, Journal of Computational Neuroscience.

[42]  Effects of Odorant Mixtures on Olfactory Receptor Cells a , 1987, Annals of the New York Academy of Sciences.

[43]  William S. Cain,et al.  ODOR INTENSITY: MIXTURES AND MASKING , 1975 .

[44]  M. M. Mozell,et al.  Evidence for Sorption as a Mechanism of the Olfactory Analysis of Vapours , 1964, Nature.

[45]  P. Duchamp-Viret,et al.  Single olfactory sensory neurons simultaneously integrate the components of an odour mixture , 2003, The European journal of neuroscience.

[46]  S H Snyder,et al.  The Odorant‐Sensitive Adenylate Cyclase of Olfactory Receptor Cells , 1986, The Journal of biological chemistry.

[47]  M. M. Mozell,et al.  Olfactory Discrimination: Electrophysiological Spatiotemporal Basis , 1964, Science.

[48]  W S Cain,et al.  Comparison of models of odor interaction. , 1995, Chemical senses.

[49]  K. Touhara,et al.  Enzymatic Conversion of Odorants in Nasal Mucus Affects Olfactory Glomerular Activation Patterns and Odor Perception , 2010, The Journal of Neuroscience.

[50]  Rainer W Friedrich,et al.  Processing of Odor Mixtures in the Zebrafish Olfactory Bulb , 2004, The Journal of Neuroscience.

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

[52]  Alan Carleton,et al.  Dense representation of natural odorants in the mouse olfactory bulb , 2012, Nature Neuroscience.

[53]  D. Restrepo,et al.  Variability of position of the P2 glomerulus within a map of the mouse olfactory bulb , 2001, The Journal of comparative neurology.

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

[55]  Hitoshi Sakano,et al.  Continuous and Overlapping Expression Domains of Odorant Receptor Genes in the Olfactory Epithelium Determine the Dorsal/Ventral Positioning of Glomeruli in the Olfactory Bulb , 2005, The Journal of Neuroscience.

[56]  Stuart Firestein,et al.  A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium , 2004, The Journal of physiology.

[57]  Thomas A. Cleland,et al.  The anatomical logic of smell , 2005, Trends in Neurosciences.

[58]  M. M. Mozell,et al.  Chromatographic Separation of Odorants by the Nose: Retention Times Measured across in vivo Olfactory Mucosa , 1973, Science.

[59]  Takashi Kurahashi,et al.  Mechanism of Signal Amplification in the Olfactory Sensory Cilia , 2005, The Journal of Neuroscience.

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

[61]  Hiroshi Kataoka,et al.  Olfactory receptor antagonism between odorants , 2004, The EMBO journal.

[62]  D. G. Laing,et al.  Odour mixture suppression: evidence for a peripheral mechanism in human and rat , 1987, Brain Research.