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Innate versus learned odour processing in the mouse olfactory bulb


The mammalian olfactory system mediates various responses, including aversive behaviours to spoiled foods and fear responses to predator odours. In the olfactory bulb, each glomerulus represents a single species of odorant receptor. Because a single odorant can interact with several different receptor species, the odour information received in the olfactory epithelium is converted to a topographical map of multiple glomeruli activated in distinct areas in the olfactory bulb. To study how the odour map is interpreted in the brain, we generated mutant mice in which olfactory sensory neurons in a specific area of the olfactory epithelium are ablated by targeted expression of the diphtheria toxin gene. Here we show that, in dorsal-zone-depleted mice, the dorsal domain of the olfactory bulb was devoid of glomerular structures, although second-order neurons were present in the vacant areas. The mutant mice lacked innate responses to aversive odorants, even though they were capable of detecting them and could be conditioned for aversion with the remaining glomeruli. These results indicate that, in mice, aversive information is received in the olfactory bulb by separate sets of glomeruli, those dedicated for innate and those for learned responses.

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Figure 1: Odorant receptor gene expression and glomerular map formation in the ΔD and ΔII mutant mice.
Figure 2: Odour maps for aversive odorants.
Figure 3: Recognition tests for innate odour qualities.
Figure 4: Discrimination tests with structurally related odorants.
Figure 5: 2MB-acid- and TMT-evoked neural pathways in the brain.


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We thank R. Sprengel for the pBS-iCre vector, J. R. Sanes for the Thy1-YFP-G mouse and Tama Zoo for the snow leopard’s urine. We also thank Y. Maruyama and A. Kawai for technical assistance. We are grateful to P. Mombaerts, J. Ngai, T. Yamamori and members of our laboratory for comments. This work was supported by the CREST program of the Japan Science and Technology Agency; the Mitsubishi Foundation; and the Special Promotion Research Grant from the Ministry of Education, Science and Culture of Japan. R.K. is supported by the PRESTO program of the Japan Science and Technology Agency.

Author Contributions K.K. and R.K. planned and performed most of the experiments. Optical imaging of intrinsic signals and mitral cell labelling were done by H.M. and K.M. Y.O. participated in the initial characterization of the O-MACS→cre knock-in mouse. T. Imai generated the MOR23→cre transgenic mouse. M.I. and M.O. helped generate the O-MACS→cre mouse. T. Ikeda and S.I. generated the Eno2-STOP-DTA mouse. T.K. advised on the behavioral analysis. H.S. supervised the project. The manuscript was written by K.K., R.K. and H.S.

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Correspondence to Hitoshi Sakano.

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Supplementary information

Supplementary Figures

This file contains Supplementary Figures S1-S11 with Legends and Supplementary Video legend. (PDF 3326 kb)

Supplementary Video

This file contains Supplementary Video 1 showing the response of δD mouse to a predator odor, TMT. (MOV 5384 kb)

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Kobayakawa, K., Kobayakawa, R., Matsumoto, H. et al. Innate versus learned odour processing in the mouse olfactory bulb. Nature 450, 503–508 (2007).

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