(Philadelphia, PA) - In a mouse model, University
of Pennsylvania School of Medicine researchers discovered
that olfactory sensory neurons expressing the same receptor responded
to a specific odor with an array of speeds and sensitivities, a
phenomenon previously not detected in the mammalian sense of smell.
The group published their findings this week in the online edition
of the Proceedings of the National Academy of Sciences.
assumed that the sensory neurons that express the same receptor
would respond to a specific odor in the same way,” says senior
author Minghong Ma, PhD, Assistant Professor of
Neuroscience at Penn. “But in real biology, these olfactory
neurons keep regenerating, and even though they all express the
same receptor, they’re probably at different states of maturation,
displaying different qualities. By knowing that olfactory neurons
can respond differently, we’re adding another layer to understanding
how the olfactory system receives outside information.”
Ma’s group measured 53 different olfactory neurons that express
the MOR23 odor receptor. As a group, the neurons reacted differently
from one another in their response to lyral, an artificial odor
used in fragrances and flavoring. After subjecting all cells to
a short pulse (200-300 milliseconds) of lyral, the researchers measured
the cells’ sensitivity to the odor. Some cells responded to
very low concentrations of lyral; others, to higher concentrations.
Regarding the cells’ reaction time, some neurons finished
firing within 500 milliseconds, but for others, the response time
was up to five seconds.
Detection of odor molecules depends on about 1000 different odor
receptors in the rodent nose. Different sets of receptors respond
to different sets of odors. To date, no one has been able to record
electrical impulses from a specific subtype of olfactory sensory
neuron expressing a known receptor. This is important, says Ma,
because prior to this paper, when researchers would work with olfactory
cells, there was no way to know what odor receptor that cell expressed.
“It could literally be one out of 1000,” she says.
All the sensory neurons expressing the same receptor merge to a
common region called a glomerulus, a region in the brain’s
olfactory bulb. In one bulb there are about 2000 glomeruli. (The
brain has two olfactory bulbs.) There are thousands of sensory neurons
dedicated to expressing the same receptor, and in the case of MOR23
they all merge to two glomeruli.
The researchers used genetically engineered mice that express MOR23
together with green fluorescent protein (GFP), which was generated
by colleagues from Rockefeller University. The GFP allows the investigators
to visualize the MOR23 cells separate from other neurons. They also
recorded their measurements using cells still intact within the
lining of the nose, which allows the researchers to study these
cells in their natural biochemical environment.
The researchers made their measurements from the endings of olfactory
neuron dendrites. A single dendrite extends from the cell body of
the olfactory neuron into the nasal cavity. The dendrite has a swelling
at the end called the knob, where about 10 to 15 hair-like extensions
called cilia contain the odor receptors.
Ma and colleagues are now working out the implications of their
findings. She says this study points to a more finely tuned response
in the brain to odors than previously thought. “Olfactory
neurons may be able to respond to an even wider range of odor concentrations
than we realized,” she says. The heterogeneity in odor sensitivity
and the wide response range in single cells provides new insights
into why mammals, including humans, perceive odors with unchanged
quality over a broad concentration range.
The research was supported by grants from the National Institutes
on Deafness and Other Communications Disorders and the Whitehall
Foundation. Study co-authors are Xavier Grosmaitre from Penn, Anne
Vassalli and Peter Mombaerts from Rockefeller University, and Gordon
Shephard from Yale University.
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