Changes in the activity of olfactory sensory neurons in the nose of a mouse before (top) and after (bottom) an odor is introduced have been recorded as changes in light intensity. Credit: Kyushu University

Take a sniff of a freshly poured glass of wine, and the prevailing scientific thinking would suggest that the harmony of fragrances involves sensory receptors in the nose simply adding up the individual odors they encounter. However, new research from Kyushu University shows that a much more complex process is occurring, with some responses being enhanced and others inhibited depending on the odors present.

In mammals, the sense of smell starts with the detection of odors by receptors at the ends of special cells—called —in the nose. Each of these has just one type of receptor out of a large repertoire that depends on the species, with humans having around 400 types and mice around 1,000.

While the brain's processing of sensory information is known to be important for picking out and synthesizing smells, relatively little is still known about the processes happening where the odors are first detected in the nose.

Using recently developed techniques for highly sensitive recording of the response of the receptors in the noses of living mice, the research group led by Takeshi Imai, professor in the Graduate School of Medical Sciences at Kyushu University, has now published in Cell Reports a deeper understanding of how neurons in the nose react to odors and their mixtures.

"It has been previously considered that each 'activates' a specific set of , and that the response of neurons in the nose to odor mixtures is a simple sum of the responses to each component, but now we have evidence in mice that this is not the case," says Shigenori Inagaki, the lead author of the paper.

A recording of the activity of olfactory sensory neurons in the nose of a mouse. When an odor is presented, changes in activity can be seen as changes in light intensity. Measurement and analysis of such recording has led to the finding that suppression and enhancement of the response of these neurons in the nose is happening when odors are mixed, overturning traditional thinking that the response is a simple sum. The recorded area is approximately 0.5 mm by 0.5 mm. Credit: Shigenori Inagaki, Takeshi Imai, Kyushu University

Studying mice that were genetically modified to have their neurons emit depending on the amount of calcium ions in them—an indicator of activity—upon absorption of excitation light, the researchers were able to sensitively record the response of the neurons in the mice's noses using a two-photon microscope.

Based on these recordings, Imai's team found that odors could not only activate but also suppress the response of the neurons in the noses of mice, indicating are happening well before the signals reach the olfactory bulb or brain for additional processing. Furthermore, their experiments showed that mixing of odors often leads to an enhancement of response through synergy, especially when they are in relatively low concentrations, or a suppression of through antagonism, especially when they are in high concentrations.

The suppression and enhancement processes revealed by this study may explain why odor mixtures produce very different perceptual outcomes from their components, and this kind of understanding could aid in the development of methods for the rational design of olfactory experiences, from pleasant, harmonious smells to deodorizers.

"These results indicate that our perception of odors is being tuned from the very moment they are detected in the ," explains Imai. "Possibly, these findings may explain how the addition of a minor amount of an odor can have such a major effect on the perceived fragrance, or how different kinds of odor molecules in a glass of wine produce a nice harmony."

More information: Shigenori Inagaki et al, Widespread Inhibition, Antagonism, and Synergy in Mouse Olfactory Sensory Neurons In Vivo, Cell Reports (2020). DOI: 10.1016/j.celrep.2020.107814

Journal information: Cell Reports

Provided by Kyushu University