A Bouquet of Responses: Olfactory Nerve Cells
Expressing Same Receptor
Display a Varied Set of Reactions
Findings Help Researchers Revise Models of Mammalian Sense
(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.
“We 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
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
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
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.
PENN Medicine is a $2.7 billion enterprise dedicated
to the related missions of medical education, biomedical research, and
high-quality patient care. PENN Medicine consists of the University of
Pennsylvania School of Medicine (founded in 1765 as the nation's first
medical school) and the University of Pennsylvania Health System.
Penn’s School of Medicine is ranked #2 in the nation for receipt
of NIH research funds; and ranked #4 in the nation in U.S. News &
World Report’s most recent ranking of top research-oriented medical
schools. Supporting 1,400 fulltime faculty and 700 students, the School
of Medicine is recognized worldwide for its superior education and training
of the next generation of physician-scientists and leaders of academic
The University of Pennsylvania Health System comprises: its flagship hospital,
the Hospital of the University of Pennsylvania, consistently rated one
of the nation’s “Honor Roll” hospitals by U.S. News
& World Report; Pennsylvania Hospital, the nation's first hospital;
Penn Presbyterian Medical Center; a faculty practice plan; a primary-care
provider network; two multispecialty satellite facilities; and home health
care and hospice.