Our Senses: Seeing, Hearing, and Smelling The World
Our Senses: Seeing, Hearing, and Smelling The World
Our Senses: Seeing, Hearing, and Smelling The World
SEEING,
HEARING,
AND
SMELLING THE
WORLD
NEW FINDINGS
HELP SCIENTISTS
MAKE SENSE OF
OUR SENSES
The Howard Hughes Medical Institute
was founded in 1953 by the aviator-
industrialist Howard R. Hughes. Its charter
reads, in part:
“The primary purpose and objective of the
Howard Hughes Medical Institute shall be
the promotion of human knowledge within
the field of the basic sciences (principally
the field of medical research and medical
education) and the effective application
thereof for the benefit of mankind.”
I
t is a pleasure to introduce the latest of the biomedical research
reports that the Howard Hughes Medical Institute publishes for
general readers. Seeing, Hearing, and Smelling the World, like
the four previous publications in the series, takes us to the frontiers
of science. It guides us on a journey into the fascinating world of the
senses and the nervous system, where researchers are working to
understand problems of great potential benefit.
The most routine, everyday occurrences, such as recognizing a
friend on the street and exchanging greetings, demonstrate the bio-
logical complexity of the puzzles that scientists are attempting to
solve. Although such encounters seem simple, they require hun-
dreds of millions of cells to act in precise ways to receive the sights
and sounds and translate them into electrical impulses. These
impulses flow through the nervous system to carry the messages to
the brain, where they can be understood and acted upon at aston-
ishing speed.
Centuries of effort by thousands of scientists in laboratories
throughout the world have been required to bring us to our current,
deepening understanding about how we hear, see, and smell.
Thanks to the new analytical tools provided by molecular biology,
progress toward understanding the senses and the nervous system
has been rapid during the past decade. Indeed, many neuroscien-
tists believe that biomedical science is poised to make substantial
progress toward understanding how the brain works, not only in
terms of the senses, but also complex functions like learning and
memory. It is an exciting prospect.
This series is published by the Institute as a public service in
order to make the results of current biomedical research available
to readers who are not scientists. It is clear that a basic grasp of
biology is increasingly essential for citizens who have to make diffi-
cult decisions about health care, drug abuse, the environment, and
other critical issues.
Teachers are particularly enthusiastic about these reports, and
surveys tell us that they preserve their copies and use them year
after year. Nearly 4,000 class sets have been requested by high
school, college, and even medical school teachers in the United
States and abroad; altogether, more than 400,000 copies of the
publications have been printed.
The Institute’s interest in science education continues to deepen
and its commitment to education reform to grow. Its grants pro-
gram, which was established in 1987, has now become the largest
private science education effort in U.S. history. Through its finan-
cial support and other activities, the Institute is seeking to make
science come alive for today’s students, which is exactly what we
hope Seeing, Hearing, and Smelling the World will do.
Taste
Hearing
Smell
Vision
A LIFE-SIZE
HUMAN BRAIN
Each of the five senses activates a
separate area of the cerebral cortex, the
sheet of neurons that makes up the outer
layer of the brain’s hemispheres. This
brain, shown in actual size, is a computer
reconstruction based on data from mag-
netic resonance imaging (MRI).
Approximate locations of the primary
sensory areas are shown in color.
Most of the activity takes place within
convolutions that cannot be seen
from the surface of the brain.
W
e can recognize a friend instantly—full-
open our eyes or ears and let the world stream in.
The shaded circles seem to form an X made of Are these triangles real? They appear to be,
spheres. But if you turn the page upside because the brain automatically fills in lines
down, the same circles form an X made of that are missing. But if you block out parts of
cavities, since the brain assumes that light the picture, the triangles vanish.
comes from above.
Gaetano Kanizsa. If you hide part of this each of these senses is precious and almost
picture, depriving the brain of certain clues irreplaceable—as we discover, to our sor-
it uses to form conclusions, the large white row, if we lose one. People usually fear
triangle disappears. blindness above all other disabilities. Yet
We construct such images unconsciously deafness can be an even more severe handi-
and very rapidly. Our brains are just as fer- cap, especially in early life, when children
tile when we use our other senses. In learn language. This is why Helen Keller’s
moments of anxiety, for instance, we some- achievements were so extraordinary. As a
These famous maps by Wilder Penfield show that each part of the body is represented on two strips of the
brain’s cerebral cortex, the somatosensory cortex (left), which receives sensations of touch, and the motor
cortex (right), which controls movements. Fingers, mouth, and other sensitive areas take up most space
on both maps. Penfield called these cross sections the “sensory homunculus” and the “motor homunculus.”
Meissner
Corpuscle
Free Nerve
Ending
Rod Cone
Rod and cone cells in the eye respond to elec- Taste receptor cells on the tongue and back
tromagnetic radiation—light. of the mouth respond—and bind—to chemi-
The ear’s receptor neurons are topped by cal substances.
hair bundles that move in response to vibra- Meissner corpuscles are specialized for
tions—sound. rapid response to touch, while free nerve end-
Olfactory neurons at the back of the nose ings bring sensations of pain.
respond—and bind—to odorant chemicals .
Light
Ion Channel
Rhodopsin
Cyclic GMP
Open Channel Closed Channel
Enzyme
Almost at the very instant that light hits a cell in where light is absorbed, to the cell’s surface mem-
the retina, or a sound wave nudges the tip of a brane, which contains a large number of channels
receptor cell in the ear, the receptor cell converts that control the flow of ions (charged atoms) into
this stimulus into an electrical signal—the lan- the cell. As ions move into the cell, they alter its
guage of the brain. electrical potential.
This conversion, or transduction, is swift and “In the dark, the channels are constantly open
precise. But it is also surprisingly intricate—so because of a high level of cyclic GMP. This allows
intricate that the process is not yet fully under- sodium and calcium ions, which carry positive
stood for most of the senses. In the past decade, charges, to flow into the cell,” explains King-Wai
however, it has been worked out quite thoroughly Yau, an HHMI investigator at the Johns Hopkins
for vision. University School of Medicine who played an
It begins when a photon of light meets one of important role in deciphering the transduction
the photoreceptor cells of the retina (either a rod process. “But in the light, the channels close. Then
or a cone cell). A photon that strikes a rod cell is the electrical potential inside the cell becomes
immediately absorbed by one of the 100 million more negative. This reduces the amount of neuro-
molecules of a receptor protein—rhodopsin—that transmitter that is released from the base of the
are embedded in the membranes of a stack of cell to act on other cells”—and thus alerts neurons
disks in the top part, or “outer segment,” of each in the next layer of retinal cells that a photon of
cell. These rhodopsin molecules have a snakelike light has arrived.
shape, crisscrossing the membrane seven times, This complex cascade of transduction events is
and contain retinal (a form of vitamin A), which repeated in a remarkably similar way in olfactory
actually absorbs the light. In the dark, the retinal receptor cells, which respond to odors, says Yau.
fits snugly into a binding pocket in rhodopsin. But the receptor cells that respond to sound use a
But on exposure to light, it straightens out. This very different system: their channels open and
alters the three-dimensional structure of the close as a direct response to a mechanical force—
entire rhodopsin molecule, activating it and trig- either tension or relaxation.
gering a biochemical cascade. Whatever the means, the end result of trans-
The activated rhodopsin then stimulates duction is the same: the cell generates an electri-
transducin, a protein that belongs to the large cal signal that flashes through a dense thicket of
family of so-called G proteins. This in turn acti- nerve cell connections in the brain, bringing news
vates an enzyme that breaks down cyclic GMP, a from the outside world in a Morse-code-like lan-
“second messenger,” dramatically lowering its guage the brain can understand.
level. Cyclic GMP carries signals from the disks,
toward you. You see its color, shape, and motion all
characteristics separately.
by Geoffrey Montgomery
Fovea
Primary
Visual
Cortex (V1)
Light
other hand, reflects the blue end of the spec- ed that this was not an intrinsic property of
trum and absorbs the red. light, but arose from the combined activity
Thinking about Newton’s discovery in of three different “particles” in the retina,
1802, the physician Thomas Young, who each sensitive to different wavelengths.
later helped decipher the hieroglyphics of We now know that color vision actually
the Rosetta Stone, concluded that the retina depends on the interaction of three types of
could not possibly have a different receptor cones—one especially sensitive to red light,
for each of these wavelengths, which span another to green light, and a third to blue
the entire continuum of colors from violet to light. In 1964, George Wald and Paul Brown
red. Instead, he proposed that colors were at Harvard and Edward MacNichol and
perceived by a three-color code. As artists William Marks at Johns Hopkins showed that
knew well, any color of the spectrum (except each human cone cell absorbs light in only one
white) could be matched by judicious mixing of these three sectors of the spectrum.
of just three colors of paint. Young suggest- Wald went on to propose that the recep-
normal gene on one chromosome can often Rhodopsin, the Nathans found that the DNA sequences of
make up for a defective gene on the other.) receptor protein in rod the genes for red and green receptors differ
Wald and others had found that in color- cells, crosses the disk by only 2 percent—evidence of their common
blind men, the green or red cones worked membrane seven origin and recent divergence.
improperly or not at all. Wald suggested that times; its odd shape is Nathans himself is not color-blind. Before
the genes for the red and green receptors shared by the three using his own DNA, he thoroughly tested his
were altered in these men. He also thought receptor proteins in color vision to ensure that it was normal.
that these genes must lie near each other on cone cells. Retinal Nevertheless, one of his initial findings pre-
the X chromosome. This tandem arrange- (which absorbs light) sented a puzzle: Lying head to tail along his
ment—which Nathans confirmed—probably is shown in purple. X chromosome were not just the two genes
results from the duplication of a DNA frag- The other colored for the red and green receptors, but also an
ment in primates that occurred some 40 mil- balls represent amino extra copy of the green receptor gene.
lion years ago. The New-World monkeys of acids that make Here was the explanation for the preva-
South America, which broke from the conti- up the rhodopsin lence of color blindness, he realized.
nent of Africa at about that time, possess structure. Because the DNA sequences of the red and
only a single functional copy of a red or green green receptor genes are so similar, and
gene, much like color-blind men. But in Old because they lie head to tail, it is easy for
World primates—the monkeys and apes of mistakes to occur during the development of
Africa and the ancestors of humans—a pri- egg and sperm, as genetic material is repli-
mordial red-green gene must have duplicat- cated and exchanged between chromosomes.
ed and then diverged slightly in sequence, One X chromosome—like Nathans’—may
leading to separate receptors of the red and receive an extra green receptor gene, for
green type. In keeping with this picture, instance, or maybe even two. This does no
A healthy retina (below), as seen through an ophthalmo- at the periphery. Cells laden with the black pigment
scope, has a firm, regular structure. In the retina of a melatonin invade the dead retinal tissue, producing
person with retinitis pigmentosa (right), cells die, starting black deposits that are characteristic of the disease.
Laboratory of Samuel Jacobson, University of Miami (2)
MO
VE
The patient had great difficulty
pouring coffee into a cup. She could
clearly see the cup’s shape, color,
and position on the table, she told
her doctor. She was able to pour the street and then upon her, without
coffee from the pot. But the column ever seeming to occupy the interven-
of fluid flowing from the spout ing space.
appeared frozen, like a waterfall Even people milling through a
turned to ice. She could not see its room made her feel very uneasy, she
motion. So the coffee would rise in complained to Josef Zihl, a neuropsy-
the cup and spill over the sides. chologist who saw her at the Max tors and their prey depend upon
More dangerous problems arose Planck Institute for Psychiatry in being able to detect motion rapidly.
when she went outdoors. She could Munich, Germany, in 1980, because In fact, frogs and some other
not cross a street, for instance, “the people were suddenly here or simple vertebrates may not even
because the motion of cars was there but I did not see them moving.” see an object unless it is moving. If
invisible to her: a car was up the The woman’s rare motion blind- a dead fly on a string is dangled
ness resulted from a stroke that motionlessly in front of a starving
BY damaged selected areas of her brain. frog, the frog cannot sense this
GEOFFREY What she lost—the ability to see winged meal. The “bug-detecting”
MONTGOMERY objects move through space—is a key cells in its retina are wired to
aspect of vision. In animals, this abil- respond only to movement. The frog
ity is crucial to survival: Both preda- might starve to death, tongue firm-
ly folded in its mouth, unaware that
salvation lies suspended on a string
in front of its eyes.
SEEING HEARING
WORDS WORDS
A GIANT MAGNET
REVEALS THE
BRAIN’S ACTIVITY
Much excitement surrounds a newer tech-
nique, fMRI, that needs no radioactive materi-
als and produces images at a higher resolution
than PET. In this system, a giant magnet sur-
rounds the subject’s head. Changes in the
direction of the magnetic field induce hydrogen
atoms in the brain to emit radio signals. These
signals increase when the level of blood oxygen
goes up, indicating which parts of the brain are
most active.
Since the method is non-invasive,
researchers can do hundreds of scans on the
same person and obtain very detailed informa-
tion about a particular brain’s activity, as well
as its structure. They no longer need to average
the resuts from tests on different subjects,
whose brains are as individual as fingerprints.
U R
Q i e iNg
V
BUNDLES
THAT LET US
HEAR
BY
JEFF GOLDBERG
of rock-and-roll.
is hot on the trail of a genetic error that appears to scientists need to work with animal models. Duyk’s
be responsible for the Bedouin tribe’s deafness. research group is presently studying two strains of
Meanwhile, David Corey and his colleague Xan- mice, called “jerkers” and “shakers,” that have been
dra Breakefield at Massachusetts General Hospital found to suffer from inherited forms of progressive
are examining the gene that is defective in Norrie hearing loss (as well as the peculiar movement disor-
disease, a different disorder that causes not only a ders that give them their names.) The researchers are
progressive loss of hearing similar to that of the looking for fragments of DNA from these mice that
Worcester family but, in addition, blindness at birth. might be similar to pieces of DNA from families with
The scientists are now analyzing the protein made genetic deafness.
by normal copies of this gene and trying to under- “We would like to develop new kinds of treatment
stand its function, which might lead to ways of pre- for hearing loss,” Duyk explains. “But first we need to
venting the disorder. identify the proteins and genes that are essential to
For a deeper understanding of such disorders, hearing.”
,,
A CHANNEL.
In this sketch, James
Hudspeth suggests how
the movement of a hair
cell’s cilia bundle (top)
opens ion channels at
the tips of the cilia. When
the bundle tilts to the right, tip links from
higher cilia pull up the gates of ion chan-
nels on adjoining, shorter cilia.
A close-up shows how a tip link between
two cilia opens an ion channel on the shorter cilium.
Even more highly magnified (right), the open channel allows ions
into the cell. A cluster of myosin molecules in the taller cilium is
shown in green and some actin filaments are shown in blue.
without any flicker. Contrast 24 frames per physical theory to account for the hair cells’
second with 20,000 cycles per second. The rapid response. But their theory didn’t tell
auditory system is a thousand times faster.” them where the channels were or what the
spring was.
How do hair cells do this? By painstakingly measuring the electri-
Unlike other types of sensory receptor cells, cal field around the cilia with an electrode,
hair cells do not rely on a cascade of chemical Hudspeth detected a tiny drop in voltage at
reactions to generate a signal. Photoreceptor the cilia’s tips, as if the current were being
cells in the eye, for instance, require a series sucked into a minute whirlpool. This led
of intricate interactions with a G protein and him to conclude that the channels through
a second messenger before their ion channels which charged particles move into the cell,
close, sending a signal to the brain. This pro- changing its electrical potential, were locat-
cess would be much too slow to deal with ed at the cilia’s tips. He then reasoned that
sounds. Hair cells have to possess a mecha- the gating springs that opened these chan-
nism that allows their ion channels to open nels should be there as well.
and close more rapidly than those of any The springs themselves were first
other sensory receptor cells. observed in 1984, in electron microscope
The answer is that hair cells use some- images taken by James Pickles and his col-
thing very much like a spring to open their leagues in England. Called tip links, these
channels when the cilia bend, without the minute filaments join each stereocilium to
need for a time-consuming chemical exchange. its tallest neighbor. Pickles pointed out that
Corey and Hudspeth first theorized that the geometry of the cilia bundle would cause
such a “gating spring” mechanism existed in the bundle to stretch the links when it was
the early 1980s. They proposed that hair deflected in one direction and relax them
cells had a previously unknown type of ion when it was moved in the other. If the tip
channel—a channel directly activated by links were the hypothetical gating springs,
mechanical force. They also developed a bio- it would explain everything.
A M OUSE
BY ITS
SOUND
BY JEFF GOLDBERG
S EEING , H EARING AND S MELLING THE W ORLD • 42
While some scientists investigate the mystery
of how we hear from the bottom up, beginning
with the ear’s sound receptors, others search for
answers from the top down, mapping networks
of auditory neurons in the brain in an effort to
understand how the brain processes sounds.
At Caltech in the mid-1970s, Masakazu
(“Mark”) Konishi began studying the auditory
system of barn owls in an effort to resolve a
seemingly simple question: Why do we have two
ears?
While most sounds can be distinguished quite
well with one ear alone, the task of pinpointing
where sounds are coming from in space requires
a complex process called binaural fusion, in
which the brain must compare information
received from each ear, then translate subtle dif-
ferences into a unified perception of a single
sound—say a dog’s bark—coming from a partic-
ular location.
Konishi, a zoologist and expert on the ner-
vous system of birds, chose to study this
process in owls. The ability to identify
where sounds are coming from based on
auditory cues alone is common to all
hearing creatures, but owls—espe-
cially barn owls—excel at the task.
These birds exhibit such extraor-
dinary sound localization abili-
ties that they are able to hunt
in total darkness.
In total darkness,
a barn owl swoops
down on a mouse.
Dan Feldman, an Working with Eric Knudsen, who is now 10,000 in all—which would fire only when
HHMI predoctoral conducting his own research on owls at sounds were presented in a particular loca-
fellow in Eric Stanford University, Konishi undertook a tion. Astonishingly, the cells were organized
Knudsen’s lab, wears series of experiments on owls in 1977 to in a precise topographic array, similar to
protective gloves as identify networks of neurons that could dis- maps of cells in the visual cortex of the
he prepares an owl tinguish sounds coming from different loca- brain. Aggregates of space-specific neurons,
for an experiment tions. He used a technique pioneered by corresponding to the precise vertical and
that will record the vision researchers, probing the brains of horizontal coordinates of the speaker, fired
owl’s head-turning anesthetized owls with fine electrodes. With when a tone was played at that location.
movements in the electrodes in place, a remote-controlled “Regardless of the level of the sound or
response to sounds. sound speaker was moved to different loca- the content of the sound, these cells always
tions around the owl’s head along an imagi- responded to the sources at the same place
nary sphere. As the speaker moved, imitat- in space. Each group of cells across the cir-
ing sounds the owl would hear in the wild, cuit was sensitive to sound coming from a
the investigators recorded the firing of neu- different place in space, so when the sound
rons in the vicinity of the electrodes. moved, the pattern of firing shifted across
Over the course of several months, Kon- the map of cells,” Knudsen recalls.
ishi and Knudsen were able to identify an The discovery of auditory brain cells that
area in the midbrain of the birds containing could identify the location of sounds in
cells called space-specific neurons—about space quickly produced a new mystery. “The
– +
Parts of a volunteer’s brain were activated (white box on left of first picture) when he heard a series of sharp but
meaningless clicks while inside a fMRI magnet at Massachusetts General Hospital. Some of the same
areas became much more active and several new areas were activated as well (square box on right of second picture)
when he listened to instrumental music, reflecting the richer meaning of the sounds.
movements, Konishi and his assistants turned its head when phantom sounds were
showed that the owls would turn toward a played. “Each neuron was set to a particular
precise location in space corresponding to combination of interaural time and intensi-
the interaural time and intensity differences ty difference,” Konishi recalls.
in the signals. This suggested that owls fuse Konishi then decided to trace the path-
the two sounds that are delivered to their ways of neurons that carry successively
two ears into an image of a single source—in more refined information about the timing
this case, a phantom source. and intensity of sounds to the owl’s mid-
“When the sound in one ear preceded that brain. Such information is first processed in
in the other ear, the head turned in the direc- the cochlear nuclei, two bundles of neurons
tion of the leading ear. The longer we delayed projecting from the inner ear. Working with
delivering the sound to the second ear, the Terry Takahashi, who is now at the Univer-
further the head turned,” Konishi recalls. sity of Oregon, Konishi showed that one of
Next, Konishi tried the same experiment the nuclei in this first way station signals
on anesthetized owls to learn how their only the timing of each frequency band,
brains carry out binaural fusion. Years ear- while the other records intensity. The sig-
lier, he and Knudsen had identified space- nals are then transmitted to two higher-
specific neurons in the auditory area of the order processing stations before reaching the
owl’s midbrain that fire only in response to space-specific neurons in the owl’s midbrain.
sounds coming from specific areas in space. One more experiment proved conclusive-
Now Konishi and his associates found that ly that the timing and intensity of sounds
these space-specific neurons react to specific are processed along separate pathways.
combinations of signals, corresponding to When the researchers injected a minute
the exact direction in which the animal amount of local anesthetic into one of the
S
“ uddenly which on Sunday mornings...my Aunt
Leonie used to give me, dipping it first in her
own cup of tea....Immediately the old gray
To make matters worse, very little was
known about the substances to which the
olfactory system responds. The average
house on the street, where her room was, human being, it is said, can recognize some
the memory rose up like a stage set...and the entire town, 10,000 separate odors. We are surrounded
with its people and houses, gardens, church, by odorant molecules that emanate from
revealed and surroundings, taking shape and solidity, trees, flowers, earth, animals, food, indus-
sprang into being from my cup of tea.” trial activity, bacterial decomposition, other
itself…” Just seeing the madeleine had not humans. Yet when we want to describe
brought back these memories, Proust noted. these myriad odors, we often resort to crude
He needed to taste and smell it. “When analogies: something smells like a rose, like
nothing else subsists from the past,” he sweat, or like ammonia. Our culture places
wrote, “after the people are dead, after the such low value on olfaction that we have
things are broken and scattered...the smell never developed a proper vocabulary for it.
and taste of things remain poised a long In A Natural History of the Senses, poet and
time, like souls...bearing resiliently, on essayist Diane Ackerman notes that it is
impalpable droplets, the immense edifice of almost impossible to explain how something
memory.” smells to someone who hasn’t smelled it.
Proust referred to both taste and smell— There are names for all the pastels in a hue,
and rightly so, because most of the flavor of she writes—but none for the tones and tints
food comes from its aroma, which wafts up of a smell.
the nostrils to sensory cells in the nose and Nor can odors be measured on the kind
also reaches these cells through a passage- of linear scale that scientists use to measure
way in the back of the mouth. Our taste the wavelength of light or the frequency of
buds provide only four distinct sensations: sounds. “It would be nice if one smell corre-
sweet, salty, sour, and bitter. Other flavors sponded to a short wavelength and another
come from smell, and when the nose is to a long wavelength, such as rose versus
blocked, as by a cold, most foods seem bland skunk, and you could place every smell on
or tasteless. this linear scale,” says Randall Reed, an
Both smell and taste require us to incor- HHMI investigator at the Johns Hopkins
porate—to breathe in or swallow—chemical University School of Medicine who has long
substances that attach themselves to recep- been interested in olfaction. “But there is no
tors on our sensory cells. Early in evolution, smell scale,” since odorous molecules vary
the two senses had the same precursor, a widely in chemical composition and three-
common chemical sense that enabled bacteria dimensional shape.
and other single-celled organisms to locate To find out how these diverse odorants
food or be aware of harmful substances. trigger our perception of smell, researchers
How we perceive such chemical sub- needed to examine the olfactory cells and
stances as odors is a mystery that, until identify the receptor proteins that actually
recently, defeated most attempts to solve it. bind with the odorants. This task was made
Anatomical studies showed that signals more difficult by the awkward location of
Taste Sensory
Cortex Olfactory
Tract
Olfactory
Bulb
Olfactory
Smell Sensory Neurons
Cortex
Taste
Receptor
cells
olfactory neuron can make only one or, at tracks for long distances over varied ter-
most, a few odorant receptors. (Buck and rain, have larger olfactory bulbs than
her colleagues have come to the same con- humans do—even though humans are more
clusion from their work with mice.) than twice the total size of these dogs and
The next step was to find out how these have brains that are several times as large.
odorant receptors—and the neurons that In the olfactory epithelium of the nose,
make them—are distributed in the nose. Axel’s group found, neurons that have a
Also, what parts of the brain do these neu- given odorant receptor do not cluster togeth-
rons connect with? “We want to learn the er. Instead, these neurons are distributed
nature of the olfactory code,” Axel says. randomly within certain broad regions of
“Will neurons that respond to jasmine relay the nasal epithelium. Then their axons con-
to a different station in the brain than those verge on the same place in the olfactory
responding to basil?” If so, he suggests, the bulb, Axel believes.
brain might rely on the position of activated “The brain is essentially saying some-
neurons to define the quality of odors. thing like, ‘I’m seeing activity in positions 1,
Each olfactory neuron in the nose has a 15, and 54 of the olfactory bulb, which cor-
long fiber, or axon, that pokes through a respond to odorant receptors 1, 15, and 54,
tiny opening in the bone above it, the cribri- so that must be jasmine,” Axel suggests.
form plate, to make a connection, or Most odors consist of mixtures of odorant
synapse, with other neurons in the olfactory molecules, so other odors would be identi-
bulb, which is a part of the brain. A round, fied by different combinations.
knob-like structure, the olfactory bulb is Buck, who has been trying to solve the
quite large in animals that have an acute same problem at Harvard, recently found
sense of smell. It decreases in relative size that the olfactory epithelium of mice is
as this ability wanes. Thus, bloodhounds, divided into regions that she calls expres-
which can follow the scent of a person’s sion zones, each of which contains a differ-
S
the ability to sense certain chemical signals pair of tiny, cigar-shaped sacs called the
emitted by people around us—without being vomeronasal organs (VNOs), where the sig-
aware of it? Many other mammals use a sep- nals are first picked up.
arate set of sensory receptor cells in their “The VNO appears to be a much more
nose to receive social and sexual information primitive structure that uses a different set
from members of their species, and there is of molecular machinery than the main olfac-
growing suspicion that we do, too.
A whiff of airborne chemicals from a
female mouse, for instance, may spur a male
ECRE
mouse to mate immediately. Certain chemi-
cal messages from other males may make
him aggressive. Other messages may pro-
A
duce changes in his physiology—as well as in
that of the responding female.
The effects of such messages would be
far less obvious in humans. If we do receive
chemical signals from people in our vicinity, tory system,” says Richard Axel, who recent-
these signals must compete with many ly became intrigued with this system. “It
other factors that influence our behavior. seems to work in a different way—and we
Yet our physiology may be just as respon- don’t know how.”
sive to chemical messages as that of other The VNOs are located just behind the
mammals. It is known that certain chemical nostrils, in the nose’s dividing wall (they
messages from other mice lead to the onset take their name from the vomer bone, where
of puberty in young males, while a different the nasal septum meets the hard palate). In
set of signals brings young female mice into rodents, at least, signals travel from the
estrus. Similarly, there are some sugges- VNO to the accessory olfactory bulb (rather
tions that women may alter their hormonal than the main olfactory bulb) and then, as
cycles when exposed to chemical signals Sally Winans of the University of Michigan
from other people. showed in 1970, to parts of the brain that
In the past five years, scientists have control reproduction and maternal behavior.
become extremely interested in these sig- “It’s an alternate route to the brain,”
nals, as well as in the “accessory olfactory explains Rochelle Small, who runs the chem-
system” that responds to them in many ani- ical senses program at the National Institute
on Deafness and Other Communicative Dis- pits—tiny openings to the VNO in the nasal
orders in Bethesda, Maryland. If the acces- septum—have been found in nearly all
sory olfactory system functions in humans patients examined by Bruce Jafek, an oto-
as it does in rodents, bypassing the cerebral laryngologist at the University of Colorado
cortex, there is likely to be no conscious at Denver, and David Moran, who is now at
awareness of it at all. the University of Pennsylvania’s Smell and
This system is particularly important to Taste Center in Philadelphia. Last year
animals that are inexperienced sexually. Thomas and Marilyn Getchell of the Uni-
Experiments by Michael Meredith, a neuro- versity of Kentucky College of Medicine in
scientist at Florida State University in Tal- Lexington and their colleagues found that
lahassee, Charles Wysocki, of the Monell the cells lining these organs have several
Chemical Senses Center in Philadelphia, molecular markers in common with the
and others have shown that the VNOs play olfactory neurons that respond to odors.
a key role in triggering sexual behavior in “This has opened up the possibility of a
naive hamsters, mice, and rats. new sensory system in humans,” says
A virgin male hamster or mouse whose Rochelle Small. “We were often told that the
vomeronasal organs are removed generally VNO does not exist in adults, so we have
will not mate with a receptive female, even taken a big step just to show that the struc-
if the male’s main olfactory nerves are ture is there.” She cautions that we still
undamaged. Apparently, the VNOs are don’t know whether this organ actually has
needed to start certain chains of behavior connections to the brain, however. “The
that are already programmed in the brain. question now,” she says, “is what its func-
Losing the VNOs has a much less dras- tion might be.”
tic effect on experienced animals, says Just what do the VNOs of rodents—or,
T S ENSE
perhaps, humans—
BY M AYA P I N E S respond to? Proba-
bly pheromones, a
kind of chemical sig-
nal originally stud-
ied in insects. The
first pheromone ever
identified (in 1956)
was a powerful sex
attractant for silk-
worm moths. A
team of German
researchers worked
20 years to isolate it.
After removing cer-
Wysocki, who has been studying the VNOs tain glands at the tip of the abdomen of
for nearly 20 years. When male mice have 500,000 female moths, they extracted a
begun to associate sexual activity with
other cues from females, including smells, IN curious compound. The minutest amount of
it made male moths beat their wings madly
they become less dependent on the VNOs. in a “flutter dance.” This clear sign that the
Sexually experienced males whose VNOs males had sensed the attractant enabled
are removed mate almost as frequently as
intact males.
THE the scientists to purify the pheromone. Step
by step, they removed extraneous matter
Do human beings have VNOs? In the and sharply reduced the amount of attrac-
tant needed to provoke the flutter dance.
early 1800s, L. Jacobson, a Danish physi-
cian, detected likely structures in a patient’s
nose, but he assumed they were non-senso-
H UMAN When at last they obtained a chemically
pure pheromone, they named it “bombykol”
ry organs. Others thought that although for the silkworm moth, Bombyx mori, from
VNOs exist in human embryos, they disap-
pear during development or remain “vesti- N OSE ? which it was extracted. It signaled, “come to
me!” from great distances. “It has been
gial”—imperfectly developed. soberly calculated that if a single female
Recently, both VNOs and vomeronasal moth were to release all the bombykol in
such as PET and fMRI cannot keep up with them. To track these messages in real
time, scientists now use faster methods—electrical recording techniques such as MEG
on large arrays of sensors or electrodes that are placed harmlessly on the scalp to
record the firing of brain cells almost instantaneously. Their data are then combined with anatomical information
THE
One of the first experiments in which structural MRI was used
brain that are activated by touching the five fingers of one hand
Llinás found this map to be distorted in the brain of a patient who had
two webbed fingers since birth. A few weeks after the man’s fingers
NEXT
Each of the color-coded areas in this combined MRI/MEG image of
the brain responds to the touch of a different finger of the right hand.
M A T C H I N G A L O C A T I O N
Comparing Comparing Updating
(High load) (Low load) (High load)
EEG Systems Laboratory, San Francisco
These computer-generated images recreate the electrical signals that flash across the brain of Only 140 milliseconds later, a dif-
a volunteer during the matching test. A strong electrical signal (first image) sweeps across ferent set of electrical signals is
the frontal cortex of her right hemisphere 320 milliseconds after a new letter has appeared on recorded from the volunteer’s brain
the screen, as she compares the letter’s location to three locations that she has seen before. and recreated in these images. This
The same areas of her brain are activated—but less intensively—in the second image, as she time the frontal cortex of her left
compares a new letter’s location to only one location that she has seen before.
Rehearsing Rehearsing
Updating
(High load) (Low load)
(Low load)
hemisphere is activated as she After the screen goes blank, the volunteer rehearses the new memory. As the
enters the location of the new letter next two images show, this activity produces yet another electrical signal over
into her working memory. The sig- her right hemisphere. The signal is stronger in the high load than in the low
nals are more intense in the high load condition, but in both cases it is maintained until a new letter appears on
load than in the low load condition. the screen.
Page Source
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4-5 Photo of head-Michael Freeman; MRI scan of brain-John Belliveau, NMR Center, 30 Vincent Clark and James Haxby, Section on Functional Brain Imaging,
Massachusetts General Hospital Laboratory of Psychology and Psychopathology, NIMH, NIH
6-7 Mark R. Holmes, ©National Geographic Society 30-31 Kay Chernush
8 Brain-John Belliveau, NMR Center, Massachusetts General Hospital 32-33 Kay Chernush
Homunculus-Reprinted with permission of Simon & Schuster, Inc. from The 34-35 John Assad, Gordon Shepherd and David Corey, Massachusetts General Hospital
Cerebral Cortex of Man by Wilder Penfield and Theodore Rasmussen ©1950 37 Michael J. Mulroy and M. Charles Liberman, Massachusetts Eye and Ear Infirmary
Macmillan Publishing Co.; renewed ©1978 Theodore Rasmussen 38 Jennifer Jordan/RCW Communication Design Inc. (adapted from a sketch by
10 Eade Creative Services, Inc./George Eade illustrator (rod and cone cells adapted James Hudspeth, HHMI, University of Texas Southwestern Medical Center)
from Scientific American Vol. 256, No. 2, page 42, 1987) 40-41 Masakazu Konishi, California Institute of Technology
11 Eade Creative Services, Inc./George Eade illustrator (rod cell adapted from 42-43 Kay Chernush
Scientific American Vol. 256, No. 2, page 42, 1987; transduction adapted from 43 Eric Knudsen, Stanford University
figure 28-3, page 404, Principles of Neural Science by Eric R. Kandel, James H. 44 Randall R. Benson and Thomas Talavage, NMR Center, Massachusetts
Schwartz and Thomas M. Jessell ©1991 Elsevier Science Publishing Company, Inc.) General Hospital
12-13 Kay Chernush 46-47 Kay Chernush
14 Instituto Cajal. CSIC. Madrid. 49 Scott T. Barrows, ©National Geographic Society
15 Eade Creative Services, Inc./George Eade illustrator (visual system adapted from a 52 Kerry J. Ressler, Susan L. Sullivan, and Linda B. Buck from Cell Vol. 73, page
drawing by Laszlo Kubinyi and Precision Graphics on page 9 of Images of Mind by 601, figure 4(5), May 7, 1993 ©Cell Press
Michael I. Posner and Marcus E. Raichle, Scientific American Library ©1994; retinal 54 The Lovers by Pablo Picasso, National Gallery of Art/Chester Dale Collection
cells adapted from a drawing by Carol Donner/Tom Cardamone Associates on page 56 Photo-The Journal of NIH Research Vol. 6, January 1994. Reprinted with
37 of Eye, Brain and Vision by David H. Hubel, Scientific American Library, ©1988) permission. Illustration-Eade Creative Services, Inc./George Eade illustrator
16 Richard H. Masland, Massachusetts General Hospital (adapted from The Journal of NIH Research Vol. 6, January 1994)
17 Eade Creative Services, Inc./George Eade illustrator (adapted from figure 28-4, 57 Urs Ribary, Rodolfo Llinás et al from the Proceedings of the National Academy
page 405, Principles of Neural Science by Eric R. Kandel, James H. Schwartz and of Sciences Vol. 90, page 3594, April 1993, ©National Academy of Sciences
Thomas M. Jessell ©1991 Elsevier Science Publishing Company, Inc.) 58 A. Gevins and M.E. Smith, EEG Systems Laboratory, San Francisco
18 Photographic Laboratory of Bascom Palmer Eye Institute, University of Miami 58-59 A. Gevins and M.E. Smith, EEG Systems Laboratory, San Francisco
19 Ann H. Milam, University of Washington, Seattle
21 Fritz Goro, Life Magazine ©Time Inc. Printing: S&S Graphics Inc.
23 Joe McNally/Sygma
26 Eade Creative Services, Inc./George Eade illustrator (adapted from a drawing by
Carol Donner on page 60 of Eye, Brain and Vision, by David H. Hubel,
Scientific American Library, ©1988)
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