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aaVol 450 | 22 November 2007 | doi:10.1038/nature06281

ARTICLES
Innate versus learned odour processing in the mouse olfactory bulb
Ko Kobayakawa1*, Reiko Kobayakawa1*, Hideyuki Matsumoto2, Yuichiro Oka1, Takeshi Imai1, Masahito Ikawa3, Masaru Okabe3, Toshio Ikeda4, Shigeyoshi Itohara4, Takefumi Kikusui5, Kensaku Mori2 & Hitoshi Sakano1
The mammalian olfactory system mediates variousresponses, 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 distinctareas 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-orderneurons 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 learnedresponses.
The mouse olfactory system can detect and discriminate diverse odorants using a repertoire of about 1,000 odorant receptor genes1. Each olfactory sensory neuron (OSN) expresses only one member of the odorant receptor gene family in a monoallelic manner2. Furthermore, OSNs expressing the same odorant receptor converge their axons to a specific set of glomeruli in the olfactory bulb3. Thus,odorous information received in the olfactory epithelium is converted to topographical maps of activated glomeruli. On the basis of the expression patterns of zone-specific markers4,5, the olfactory epithelium can be divided into two, non-overlapping areas: a dorsal zone (D zone) and a ventral zone (V zone). Vertebrate odorant receptor genes are phylogenetically divided into two distinct classes6:class I and class II. Class I odorant receptors are expressed exclusively in the D zone of the olfactory epithelium, and OSNs expressing them project their axons to the most antero-dorsal area in the olfactory bulb7,8. In addition to the class I odorant receptors, ,300 class II odorant receptors are also expressed in the D zone, but their corresponding glomeruli reside on the periphery of the classI area in the olfactory bulb. The remaining class II odorant receptors are expressed in the V zone and their glomeruli are found in the ventrolateral area in the olfactory bulb4,9. Thus, the glomerular map seems to be subdivided into three compartments along the dorso-ventral axis in the olfactory bulb: a dorsal domain for class I odorant receptors (DI domain), a dorsal domain for class IIodorant receptors (DII domain) and a ventral domain for class II odorant receptors (V domain) (Supplementary Fig. 1a). The olfactory bulb can also be divided into distinct domains in other ways, for example, on the basis of the chemical natures and structural features of odorous ligands10. Because a particular odorant interacts with many different odorant receptor species, multiple sets of glomeruli areactivated in different olfactory bulb domains11. However, little is known about how the topographical information in the olfactory bulb is transmitted to and interpreted in the brain to decode the odour map. To address these questions, we generated two new strains of mutant mice in which the OSNs in a specific area of the olfactory epithelium are ablated.
Generation of the zone-specific...