With only 32 of its 302 nerves dedicated to detecting the odors that drift
through its world, the lowly roundworm seems hard pressed to smell food, let
alone discriminate friend from foe. But researchers have discovered a unique
system of overlapping sensors that enables the creature to tell smells apart.
The system seems well designed for the nerve-challenged worm. In mice and
humans, each of millions of odor sensing nerves has only one type of odor
detecting receptor, allowing the brain to distinguish between odors by tracking
which nerve did the sensing. But in a compromise between the need to detect
many odors and the scarcity of available nerves, the roundworm’s odor sensing
neurons are studded with receptors for different odors. It has been a
biological puzzle how a nerve that senses many odors can distinguish between
Scientists at the University of California, San Francisco uncovered a clever
combination strategy in the worm’s odor sensing nerves. Paired nerves, they
found, have receptors tuned to some of the same odors, yet each member of the
pair also supports receptors tuned to unique odors not detected by the partner.
With this partially overlapping detection system, the nerve pairs can sense
more odors than would be possible if they had identical receptors or even if
each were tuned to completely different smells, the scientists found. More
importantly, the combinatorial approach allows the nerve pairs to discriminate
between different odors, a lifesaving trait if the worm has to find one source
of food in a bewildering array of aromas.
“The worm can solve amazingly complex sensory problems with few olfactory
nerves,” said senior investigator of the study, Cornelia I. Bargmann, PhD, an
investigator in the Howard Hughes Medical Institute and professor and vice
chair of anatomy at UCSF.
“Each nerve cell has a private window into the world of smells and a shared
window with its partner. Any one nerve cell can get confused, but by comparing
the private and shared information, the animal sorts out and distinguishes all
possible combinations of odors.”
The combinatorial approach may be unique to this simple creature, Bargmann
suggests, or it may be a clue to how higher organisms including humans solve
the same problem: how a sensory system or another part of the brain can process
a nearly limitless number of environmental cues with a finite number of nerves.
“We want to understand the relationship between genes, cells and behavior in
the brain,” she said, “but our own brains are complex beyond belief. In this
fairly simple animal, we can decode the ‘thinking strategy’ used by every cell
in the brain.”
The research is published in the April 5 issue of Nature. Lead author is Paul
D. Wes, PhD, a post-doctoral scientist in Bargmann’s laboratory. (In a parallel
paper in the same issue, a research group in Oregon found similar results in
the worm’s taste center, a system that is organized much like the taste system
The worm in question is C. elegans, or more elegantly, Caenorhabditis elegans,
a millimeter-long soil dweller widely studied by geneticists and developmental
biologists because it displays many developmental processes and instinctive
behaviors common to higher organisms. The worm is tiny and transparent, with a
very small brain that can be studied in detail.
The key odors of interest in the UCSF study were benzaldehyde, which gives off
a scent somewhat like almond, and butanone which has an oily smell. Both are
thought to be produced by bacteria, the worm’s food, but both can also be
pervasive smells without useful information. Under those circumstances a
sensible worm ought to ignore them, Bargmann said.
The scientists assayed a worm’s ability to distinguish between the two odors by
exposing it to a high concentration of butanone and then testing its ability to
be attracted to benzaldehyde in this odor environment.
They examined the odor sensing abilities of a pair of olfactory neurons, known
as AWC, which has been the focus of the Bargmann lab for ten years. Her
research group has determined that this nerve pair not only senses at least
five attractive odors, but can also distinguish between the odors.
The lab recently discovered that the two neurons, which had been thought to be
identical left-right members of a pair, actually differ in one subtle, but
critical respect. During the development of the nerves, an odor receptor known
as STR-2 becomes active on one of the nerves but not on the other. Whether the
receptor is expressed on the left or the right nerve is apparently random, they
Bargmann and Wes used standard techniques to search among mutant worms for
those that were unable to detect the difference between benzaldehyde and
butanone and then showed that these genetic mutants, known as ky542, possess an
active STR-2 receptor on both members of the AWC neuron pair, unlike normal
They further showed that they could induce this odor discrimination deficit in
normal worms by killing one of the paired AWC cells with a laser beam. Either
the mutant worms or the operated worms could sense both odors perfectly well,
but with a change in one of the AWC neurons, discrimination was lost. The
difference between detection and discrimination is the first step in higher
processing in the senses, Bargmann said, and the experiment showed where that
Only one of the paired AWC nerves, the one that expresses STR-2, responds to
butanone, the scientists found, while both this neuron and its STR-2-silent
partner can detect benzaldehyde. The nerve with the silenced STR-2 is required
for discrimination between butanone and benzaldehyde, because it can smell
benzaldehyde without sensing the confusing butanone odor. In turn, that
silenced nerve senses a third odor, a buttery smell, that its partner can’t
detect. So, each nerve cell can recognize smells that are either buttery or
oily but not both, and they both recognize almond-like smells. By comparing
the private and shared information, the animal can detect more odors than if
each of the paired nerves sensed entirely different smells.
The research is funded by the Howard Hughes Medical Institute and the National
Institutes of Health.