DURHAM,
NC (7/25/99)- A high resolution imaging technique developed by researchers
at Duke University that visualizes the brain in the act of sensing odors could
act as a 'Rosetta stone' for understanding olfactory processes, and the related
processes of learning and memory.
Neurological researchers use an imaging method called intrinsic signal imaging
to map brain activity in response to various stimuli. Benjamin Rubin and Lawrence
Katz refined this technique, increasing the resolution tenfold, to produce
the first detailed images of the living brain in the act of recognizing specific
odor molecules.
Working with a rodent model, the scientists obtained images of hair-thin
olfactory structures, called glomeruli, that cover the surface of olfactory
bulbs- stem-like projections in the forebrain that receive signals from the
chemical receptor cells that line the nasal passages. The imaging technique
is based on the phenomenon whereby active cells consume more oxygen, converting
oxygen-carrying oxyhemoglobin to deoxyhemoglobin. Since deoxyhemoglobin absorbs
red light more than the oxygenated form, the scientists were able to distinguish
activated glomeruli by imaging the olfactory bulbs under a red light shone
through the animal's skull. Activated glomeruli showed up as distinctive dark
spots on the images.
Photo caption:
Video images of the olfactory bulbs of the brains of rats exposed to amyl
acetate (smells like banana), peanut butter and carvone (smells like caraway).
The dark spots indicate glomeruli that are activated by the smells and thus
convert large amounts of oxyhemoglobin to deoxyhemoglobin, which absorbs more
red light.
By exposing the animals to various concentrated odors, the researchers were
able to map sensory activity in the olfactory bulb. Different areas 'lit up'
in response to chemical odorants that smelled like bananas, caraway and spearmint,
as well as the mixed-chemical smell of peanut butter. The imaging studies
showed that activation patterns in olfactory bulbs on one side of an animal's
brain matched those on the other. The studies also showed that the patterns
of activation were very similar from animal to animal.
"We found that we could visualize individual glomeruli, achieving the
best resolution anyone has obtained so far. And most exciting, we found that
we could see distinctive patterns of activated areas from different odorants.
This technique can serve as our guide, our Rosetta stone, for deciphering
the olfactory response and even helping us to understand higher olfactory
processing areas of the brain," said Dr. Katz.
As they refined the imaging technique, Katz and Rubin were able to measure
how the activation pattern of glomeruli changed as the concentration and molecular
structure of odorants changed. For example, they found that the activation
maps changed significantly as they increased the concentration of the odorant
chemical amyl acetate several thousandfold. The maps also changed when the
animals were exposed to different aromatic chemicals called aldehydes that
differed by only a couple of atoms.
"Previously, you simply couldn't compare such responses to multiple
concentrations and multiple chemicals in the same animal, because the only
technique available was to use tracers that could only detect response to
a single odorant. Also, that technique required killing the animal and doing
detailed analyses that took weeks," said Katz.
Researchers in this field have been debating whether closely related odorants
could be distinguished by spatial mapping, or whether there was some timing
of neuronal firing involved. The current research addresses this issue, showing
that it is possible to distinguish odorants just on the basis of the pattern
of activated glomeruli.
The sense of smell is critical for the processes of learning and memory.
The new olfactory visualization system offers 'high promise' in studying the
machinery of the learning process, said Katz:.
"In rodents, the olfactory system is the sensory system of choice, and
we believe we can see the early stages of learning at the olfactory bulb level.
Since our system is very rapid and noninvasive, we think it offers an extraordinary
pathway to studying learning."
The research appears in the July 1999 issue of Neuron.
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