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 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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