Sensitivity-dependent Hierarchical Receptor Codes for Odors

In order to comprehend the strategy of odor encoding by odorant receptors, we isolated 2740 mouse receptor neurons from four olfactory epithelial zones and classified them in terms of their sensitivities and tuning specificities to a chiral pair of odorants, S(+)-carvone (caraway-like odor) and R(–)-carvone (spearmint-like odor). Our approach revealed that the majority of receptors at the lowest effective stimulus concentration represented the principal odor qualities characteristic of each enantiomer by means of the principal odor qualities of the odorants for which the receptors were most sensitive. The chiral-non-discriminating receptors became 3.7 times of R(–)-carvone-sensitive receptors in the subpopulations when the stimulus concentration was increased 10-fold. More than 80% of the responsive receptors (an estimated 70 ± α types) exhibited overlapping sensitivities between the enantiomers. The signals from the non-discriminating receptors may be reduced to decode the characteristic odor identity for R(–)-carvone in the brain over an adequate range of stimulus strengths. The information processing of odors appears to involve the selective weighting of the signals from the most sensitive receptors. An analysis of the overall receptor codes to carvones indicated that the system employs hierarchical receptor codes: principal odor qualities are encoded by the most sensitive receptors and lower-ranked odor qualities by less sensitive receptors.

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

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

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

[4]  Michael Leon,et al.  Perceptual Correlates of Neural Representations Evoked by Odorant Enantiomers , 2001, The Journal of Neuroscience.

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

[6]  Linda B. Buck,et al.  Genetic tracing reveals a stereotyped sensory map in the olfactory cortex , 2001, Nature.

[7]  Hiroshi Kataoka,et al.  Molecular Bases of Odor Discrimination: Reconstitution of Olfactory Receptors that Recognize Overlapping Sets of Odorants , 2001, The Journal of Neuroscience.

[8]  L. Haberly,et al.  Parallel-distributed processing in olfactory cortex: new insights from morphological and physiological analysis of neuronal circuitry. , 2001, Chemical senses.

[9]  Lawrence C. Katz,et al.  Spatial coding of enantiomers in the rat olfactory bulb , 2001, Nature Neuroscience.

[10]  G. Laurent,et al.  Dynamic optimization of odor representations by slow temporal patterning of mitral cell activity. , 2001, Science.

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

[12]  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.

[13]  Naoshige Uchida,et al.  Odor maps in the mammalian olfactory bulb: domain organization and odorant structural features , 2000, Nature Neuroscience.

[14]  G M Shepherd,et al.  Molecular mechanisms underlying differential odor responses of a mouse olfactory receptor. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Leon,et al.  Modular representations of odorants in the glomerular layer of the rat olfactory bulb and the effects of stimulus concentration , 2000, The Journal of comparative neurology.

[16]  Hitoshi Sakano,et al.  Mutually exclusive expression of odorant receptor transgenes , 2000, Nature Neuroscience.

[17]  J. Eberwine,et al.  Expression of mRNAs Encoding for Two Different Olfactory Receptors in a Subset of Olfactory Receptor Neurons , 2000, Journal of neurochemistry.

[18]  M. S. Singer,et al.  Analysis of the molecular basis for octanal interactions in the expressed rat 17 olfactory receptor. , 2000, Chemical senses.

[19]  H. Breer,et al.  Responsiveness of olfactory neurons to distinct aliphatic aldehydes. , 2000, The Journal of experimental biology.

[20]  Cori Bargmann,et al.  The olfactory bulb: coding and processing of odor molecule information. , 1999, Science.

[21]  N. Uchida,et al.  Synchronized oscillatory discharges of mitral/tufted cells with different molecular receptive ranges in the rabbit olfactory bulb. , 1999, Journal of neurophysiology.

[22]  H. Sakano,et al.  Olfactory Neurons Expressing Closely Linked and Homologous Odorant Receptor Genes Tend to Project Their Axons to Neighboring Glomeruli on the Olfactory Bulb , 1999, The Journal of Neuroscience.

[23]  M. Laska,et al.  Enantioselectivity of odor perception in squirrel monkeys and humans. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[24]  Hanns Hatt,et al.  Specificity and Sensitivity of a Human Olfactory Receptor Functionally Expressed in Human Embryonic Kidney 293 Cells andXenopus Laevis Oocytes , 1999, The Journal of Neuroscience.

[25]  L. C. Katz,et al.  Optical Imaging of Odorant Representations in the Mammalian Olfactory Bulb , 1999, Neuron.

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

[27]  G. Beauchamp,et al.  Odortypes: their origin and composition. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Dietmar Krautwurst,et al.  Identification of Ligands for Olfactory Receptors by Functional Expression of a Receptor Library , 1998, Cell.

[29]  G. Shepherd,et al.  Imaging Odor-Induced Calcium Transients in Single Olfactory Cilia: Specificity of Activation and Role in Transduction , 1998, The Journal of Neuroscience.

[30]  J. Kauer,et al.  Odorant Response Properties of Convergent Olfactory Receptor Neurons , 1998, The Journal of Neuroscience.

[31]  R. Axel,et al.  Odorant Receptors Govern the Formation of a Precise Topographic Map , 1998, Cell.

[32]  K. Mikoshiba,et al.  Functional expression of a mammalian odorant receptor. , 1998, Science.

[33]  J. Thompson,et al.  The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. , 1997, Nucleic acids research.

[34]  L. Buck,et al.  A Multigene Family Encoding a Diverse Array of Putative Pheromone Receptors in Mammals , 1997, Cell.

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

[36]  S. Nakanishi,et al.  Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

[39]  I. Simon,et al.  Allelic inactivation regulates olfactory receptor gene expression , 1994, Cell.

[40]  Gordon M. Shepherd,et al.  Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor. , 1994, Neuroreport.

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

[42]  M. Tonoike,et al.  Simultaneous recording of [Ca2+]i increases in isolated olfactory receptor neurons retaining their original spatial relationship in intact tissue , 1992, Journal of Neuroscience Methods.

[43]  K. Imamura,et al.  Differential specificities of single mitral cells in rabbit olfactory bulb for a homologous series of fatty acid odor molecules. , 1992, Journal of neurophysiology.

[44]  M. Tonoike,et al.  Two types of increases in free Ca2+ evoked by odor in isolated frog olfactory receptor neurons. , 1991, Neuroreport.

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

[46]  T. Kurahashi,et al.  The response induced by intracellular cyclic AMP in isolated olfactory receptor cells of the newt. , 1990, The Journal of physiology.

[47]  C. Tilquin,et al.  Sensory evidence for olfactory receptors with opposite chiral selectivity , 1989, Behavioural Brain Research.

[48]  G. Ohloff Chemistry of odor stimuli , 1986, Experientia.

[49]  K. Mori,et al.  Two types of postsynaptic inhibition in pyriform cortex of the rabbit: fast and slow inhibitory postsynaptic potentials. , 1982, Journal of neurophysiology.

[50]  K. Mori,et al.  Long-lasting disinhibition in pyriform cortex of the rabbit. , 1982, Journal of neurophysiology.

[51]  P. Pelosi,et al.  Specific anosmia to l-carvone: the minty primary odour , 1978 .

[52]  L Friedman,et al.  Odor Incongruity and Chirality , 1971, Science.

[53]  D. Guadagni,et al.  Evidence for the Difference between the Odours of the Optical Isomers (+)- and (−)-Carvone , 1971, Nature.

[54]  F. Nerdel,et al.  Geruch und Konstitution , 1951 .

[55]  H. Kröper,et al.  Geruch und Konstitution (I. Mitteil.) , 1929 .

[56]  Daniel F. Klessig,et al.  Corrections and Retraction , 2004 .

[57]  F. Zufall,et al.  Amplification of odor-induced Ca(2+) transients by store-operated Ca(2+) release and its role in olfactory signal transduction. , 2000, Journal of neurophysiology.

[58]  S. Arctander,et al.  Perfume And Flavor Chemicals: (Aroma Chemicals) , 2000 .

[59]  L. Buck,et al.  Information coding in the vertebrate olfactory system. , 1996, Annual review of neuroscience.

[60]  L. J. Gemert,et al.  Sensory properties of optical isomers , 1993 .

[61]  K. Kurihara,et al.  Quantitative analysis on odor intensity and quality of optical isomers in turtle olfactory system. , 1992, The American journal of physiology.

[62]  M. Beets,et al.  3 – Odor and Stimulant Structure , 1982 .

[63]  J. Bowmaker,et al.  Visual pigments of rods and cones in a human retina. , 1980, The Journal of physiology.

[64]  J. Amoore Molecular basis of odor , 1970 .