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Pheromone Notes #24
News release issued by Howard Hughes
Medical Institute:
Researchers Record First "Pheromone
Images" in Brains of Mice
Howard Hughes Medical Institute
researchers are beginning to unravel how
a mysterious sixth sense guides animal
attraction. The scientists have made the
first-ever recordings of patterns of brain
activity in a mouse as it explores the
sex and identity of a newly encountered
animal.
The research team, led by Lawrence C.
Katz, a Howard Hughes Medical Institute
investigator at Duke University Medical
Center, recorded the firing of neurons
in the accessory olfactory bulb, part
of a poorly understood sensory pathway
that is thought to be important in sex
discrimination and social behavior in
most mammals. Katz presented his research
findings at the annual meeting of the
American Association for the Advancement
of Science in Denver, Colorado.
The results of the studies, which will
also be published in a future issue of
the journal Science, show that chemical
signals called pheromones trigger highly
specific patterns of neural excitation
in the brain. These “pheromone images”
provide vital information about the sexual
receptiveness of females and the dominance
hierarchy in males, among other things,
said Katz.
“Mice, which live in the darkness
in the wild, can readily identify each
other on the basis of a pheromonal image
rather than a visual image,” said
Katz.
Both wild and domestic animals, such
as dogs and cats, collect pheromone signals
through the “flehmen” response,
in which the upper lip curls back during
exploration of the oral and anogenital
areas of other animals during social encounters.
These pheromone signals are collected
by the vomeronasal organ (VNO), a hollow
tube in the nasal cavity. Sensory neurons
lining the VNO, in turn, stimulate neurons
in the accessory olfactory bulb, a part
of the central nervous system. Finally,
signals are sent to the amygdala, a part
of the brain responsible for basic drives,
such as fear, aggression, mating behavior
and maternal instincts.
The information contained in pheromone
signals is key to survival and reproduction,
said Katz. Male mice establish dominance
hierarchies, so they need to know if another
male is dominant or non-dominant. In addition,
males respond to females who are in estrus
because they smell different. “In
essence,” said Katz, “these
pheromonal cues help mice decide `should
I mate or fight.'”
Important clues to the VNO's importance
in sex recognition have emerged from genetic
studies. For example, HHMI investigator
Catherine Dulac and her colleagues at
Harvard University reported in January
2002 that mice lacking a key molecule
in the pheromone-signaling pathway were
unable to distinguish males from females
and behaved as if all mice were female.
To capture the pheromonal image created
by this accessory olfactory system, Katz
and his colleagues, which included Minmin
Luo of Duke and Michale Fee of Lucent
Technologies in Murray Hill, N.J., developed
miniature electrodes and micromotors to
record the firing of individual neurons
in mice that were awake and behaving normally.
The electrodes were implanted in the accessory
olfactory bulb, which along with the main
olfactory system, processes pheromone
signals. The micromotors, which are about
the size and shape of a pencil eraser,
were light and unobtrusive, so they did
not interfere with the normal activities
of the mice, said Katz. Once the recording
device was attached to the mouse, the
researchers introduced another mouse into
the cage and allowed the two to interact.
In each case, test animals repeatedly
explored the faces and anogenital areas
of the stimulus animals with their snouts.
The scientists then recorded male mouse
responses to females, males of the same
and different genetic backgrounds, and
castrated males. To be certain they were
recording responses to pheromones, the
scientists also recorded responses as
the test mice investigated fake mice,
which never evoked any neuronal response.
“No one has ever recorded from this
area because it only works while the animals
are awake and exploring their environment,”
said Katz. “What we've done is look
at how that sensory information is sent
into a central location and what kind
of information is represented in the brain.”
When they began their studies, the scientists
hypothesized that individual neurons might
be responsible for detecting “maleness”
or “femaleness,” but instead
they found a much more sophisticated sensory
system that could distinguish individuals
with great fidelity.
“The most exciting thing we found
was that individual neurons were responsive
to individual animals. Each type of animal
encountered set off a unique pattern of
neural excitation or inhibition,”
said Katz. “We did not see any neurons
that responded to all male mice or to
all female mice. They responded to the
male mice of a specific genetic identity,
but not to male mice of other genetic
backgrounds. This suggests there must
be pheromones that male mice of one genetic
identity have, but that male mice of another
genetic identity do not. In essence, each
individual animal has a different pheromonal
signature.”
“What we also learned,” he
added, “is that there must be pheromonal
signals, whose identity we do not yet
know, that carry information about sexual
identity.”
There is evidence that humans also respond
to pheromone signals, said Katz. “Don't
forget that for years the main ingredient
in perfume was a secretion from the anal
gland of the civet cat, which is probably
full of pheromones. In addition, there
is evidence in humans that pheromone-like
molecules activate different parts of
the brain than standard odorants. And
a lot of people think that kissing and
all of the other oral investigations that
humans engage in is a vestige or even
an ongoing part of this pheromone system.”
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