No Use Moving the Cheese
Superman has super-hearing. Spider-Man has an uncanny "spider
sense." But truth can be stranger than fiction. The newest
superhero doesn't wear a cape or mask. It's a mouse, and it looks
just like its normal brethren. Its super power is its amazing
… nose. In a paper published in the February 5 issue of
Neuron, collaborators at Florida State University and Yale
University describe what they call "super-smeller" mice.
These exceptional creatures have noses that are 1,000 to 10,000
times more sensitive than those of ordinary mice.
The superhero origin of these rodents involves the deletion, or
knockout, of a gene. This technique usually generates mice that are
quite sick, as nearly all mutations are harmful. Yet it doesn't seem
to be true for this gene, Kv1.3, which encodes a protein
that acts as a channel to let potassium ions (K+) into
cells. This particular ion channel is found in immunological T-cells
and neurons in the hippocampus and the olfactory bulb—the part
of the brain that gets information from odor receptors in the nose.
In neurons, K+ channels such as Kv1.3 can act
like governors on an engine, restricting the firing rate of the
electrical spikes known as action potentials. The deletion of
Kv1.3 removes this block. Using mice generated in the Yale
lab of Richard Flavell, a team at Florida State led by Debra Fadool
discovered that the loss of the channel caused one type of olfactory
neuron, the mitral cell, to fire at lower thresholds and higher
frequencies. Furthermore, the mutant cells were insensitive to
chemical messages that normally rein in the flow of electrical
current during an action potential. According to coauthor Leonard
Kaczmarek, whose group at Yale studies the ion-channel biology of
sensation, these changes resulted in greater excitability and better
timing—effectively "phase locking" the output of the
mitral cells, and thereby increasing the coherence of olfactory signals.
The mutation also caused structural changes in the olfactory bulb.
In this part of the brain, olfactory receptor cells connect to
mitral cells in clusters called glomeruli. The knockout mice had
glomeruli that were about half as large—but twice as
abundant—as normal. As a result, information from the nose
went to twice as many "processing units" as usual. Fadool
suggests this might increase the resolution of the
signal—meaning that a faint odor would be more likely to be
noticed above the jumble of background smells.
Mutant mice could distinguish between complex odors, such as
peppermint and powdered food, with nearly 15 times the sensitivity
of normal mice. They were also better at detecting subtle molecular
differences between odorants, such as some (but not all) closely
related alcohols. The most amazing change was a huge increase in
sensitivity: Mutants were able to perceive an odor that was 1,000
times more dilute than what wild type mice could smell.
The super-smeller was definitely a surprise—none of the
investigators intended to create such a creature. "We had no
inkling," states Kaczmarek. "We were looking for an effect
in the auditory system." A chance meeting between Fadool and
Kaczmarek in the mailroom of the Marine Biological Laboratory at
Woods Hole, Massachusetts, prompted the collaboration.
As for commercial applications of the mice—bomb-sniffing mice,
perhaps?—Kaczmarek says that while such droll uses have been
mentioned, the investigators haven't been approached by eager
entrepreneurs or government agents. "I don't think it would
work," he quipped. "You'd have to have the mouse on a
leash so it wouldn't get loose in the airplane." I guess
The Adventures of Super-Smeller and the Sky Marshals
will have to wait.