How To Create a Fearless Mouse

Its hard to find a more stereotyped relationship than that of the cat and mouse. The cat hunts the mouse, and the mouse fears and runs from the cat. An innate fear response can be replicated in mice just but introducing it to feline urine, which contains olfactory clues which give the mouse information about the presence of a friend or foe. And in fact, an important group of olfactory sensory cells are responsible for detecting these molecules and translating it to a behavioral response which all mice are born with. Recent research by Kobayakawa et al. has discovered that deleting this group of cells renders these mice fearless in the presence of feline urine; although they can "smell" its presence, it no longer elicits a "danger" response. However, they can be taught to fear this smell.

This is interesting as it suggests two neural pathways for olfactory information: one for "innate" fear (which normal mice show in the presence of cat urine), and one for "learned" fear (which the mutant mice show after being trained to fear the cat urine). The mouse olfactory epithelium has two major regions, dorsal and ventral, which differ greatly in the type of receptors located therein as well as where the originating neurons go. Sakano et al created a mouse strain which lacked dorsal olfactory neurons, and then examined the mice's response to 'dangerous' smells as well as benign/good smells.

Model of receptor distribution in the mouse olfactory epithelium. While normal mice contained olfactory receptors in the dorsal and ventral areas (left), the mutant mice lacked receptors in the dorsal region (right).

Normal mice exhibit an attraction to food smells and 'friend smells,', but flee from bad smells like rotten food and 'danger' smells. The mutant mice showed dampened responses to those same smells, and showed less interest behaviorally (see figure below).

I recommend looking at the figure in a separate window (View high-res image in pop-up).

As the figure above illustrates, the mutant mice spent less time investigating mouse urine and peanut butter and more time than they should have spent investigating a variety of "bad smells," like feline urine, than their normal counterparts did. The red line across the figure indicates the threshold that the investigaters used to determine whether the mice were trying to avoid the smell, or if they were attracted to it.

But, its not that they couldn't smell it at all- if the mice were consistently made ill in conjunction with a particular smell, they could learn to avoid it. This suggest that its the dorsal olfactory neurons which transmit information related to innate fear response and the ventral neurons are involved in learning aversion to smells.

Kobayakawa et al. Innate versus learned odour processing in the mouse olfactory bulb. Nature. Nov 7. doi:10.1038/nature06281