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 (Figure 1). 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 (Figure 2). 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 (Image 1,2,3). 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.
This result was published in the November 22th issue of Nature. Kobayakawa et al., Nature, Volume 450, p503-508 (2007)
Figure1: a. The olfactory epithelium is divided into two topographical areas; the dorsal zone (D zone; blue) and the ventral zone (V zone; red). The odorant receptors are categorized phylogenetically into two groups; class I and class II. Both class I and class II odorant receptors function in the D zone, whereas only class II odorant receptors function in the V zone. It is known that the glomeruli of similar nature tend to gather, and make some domain structures on the olfactory bulb. There are dorsal-class I (DI; green) and dorsal-class II (DII; blue) domains on the dorsal part of the olfactory bulb, and there is a ventral (V; red) domain on the ventral part of the olfactory bulb. The olfactory sensory neurons, in which the same kind of odorant receptor functions, fasciculate their axons on the same glomerulus.
b. The left photo shows the mouse, which sniffs and is attracted to food odors. The right photo shows the moue, which sniffs and shows fear response to one component (TMT) of the smell of fox, a natural predator to mice. The figures schematically illustrate the patterns of glomeruli, which are activated by each odorants (odor maps).
Figure2: a. Generation of the dorsal zone-depleted (△D) mouse. We made use of O-MACS promoter, which specifically functions in the dorsal zone of the olfactory epithelium, to activate the Cre recombinase specifically in this area. The Cre recombinase has the nature to delete intervening sequences between two loxP signals (indicated by black triangles). Only when the STOP sequences between two loxP signals are deleted by Cre recombinase, the diphtheria toxin gene is activated in a neuron-specific manner. Therefore, only the olfactory sensory neurons in the dorsal zone of the olfactory epithelium are selectively removed from the nasal cavity.
b. Generation of the class II-depleted (△II) mouse. We made use of MOR23 promoter, which functions specifically in the class II olfactory sensory neurons, to activate the Cre recombinase specifically in this type of neurons. Only class II olfactory sensory neurons, in which the diphtheria toxi gene is activated, are selectively removed from the nasal cavity.
Image1: Trimethylthiazoline (TMT) is secreted from anal gland of fox. Wild type mice show avoidance responses to TMT. However the mutant mice did not demonstrate any avoidance responses to TMT.
