By JULIET ISSELBACHERJUNE 18, 2020

New research untangles the complex code the brain uses to distinguish between a vast array of smells, offering a scientific explanation for how it separates baby powder from bleach, lemon from orange, or freshly cut grass from freshly brewed coffee.

A single scent can trigger a complex chain of events in what’s known as the olfactory bulb, the brain’s control center for smell. To unravel the intricacies of that process, researchers in the U.S. and Italy turned to a technique known as optogenetics, which uses light to control neurons in the brain. In research on mice, they used light to trick the brain into thinking it smelled a particular scent, then studied brain activity to understand the role different neurons play in a mouse’s ability to recognize that scent. Their findings were published Thursday in Science.

When we encounter a certain smell, it stimulates a specific pattern of activity among tiny spheres known as glomeruli, which are found in the olfactory bulb. The odor plays across these glomeruli like a melody across piano keys: Just as a tune is made distinct by which keys are pressed and at what point in the melody, a scent is made distinct by which glomeruli are activated and in what order.

A tune remains identifiable even with some tweaks: We can still place a melody marred by a wrong note or a mistimed beat. Likewise, we can still recognize a scent altered by some change in its characteristic activity pattern. The researchers wanted to understand how the specific combination of neurons that respond to a scent — including where they’re located, and when they’re activated — might affect whether the brain registers a smell as recognizable.

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To do so, the researchers harnessed optogenetics to activate genetically engineered, light-sensitive neurons. The scientists used light to stimulate a specific pattern across glomeruli in mouse brains, which gave the mice the experience of smelling a particular scent — even though that scent that did not actually exist outside of their own heads.

“You can do this experiment with the music. I’ll play different music and see which notes are more important, less important,” said Dmitry “Dima” Rinberg, a neuroscientist at NYU Langone Health and a senior author of the study. “We asked not on the level of the external stimulus, but at the level of stimulating neurons.”

The scientists trained the mice to respond in a particular way to this “synthetic smell.” Then, they introduced different tweaks to that pattern — like wrong notes in the melody — and watched to see which of those changes affected whether a mouse could still “smell” the scent.

Justus Verhagen, Yale researcher who studies taste and smell and was not involved in the research, said that the new paper builds on past research into the locations of olfactory neurons and the timing of their activation by bringing the two factors together into a single, comprehensive model

“The difference in the perception seems to follow fairly linearly with the magnitude of the change in either space or time of the stimulation of the olfactory system,” he said. “That linearity is kind of surprising because, in neuroscience, we’re very used to a lot of nonlinear effects.”

The study also cemented the findings of previous research, which has shown that receptors activated earlier are more essential to scent recognition than those activated later on.

“If I messed up with the first note, you have a much higher chance to misinterpret the melody than if I messed up with the 25th note,” Rinberg explained. That makes sense from an evolutionary perspective, he added — animals out in the wild need to make instantaneous assessments of danger. It’s what’s known as the primacy effect. Rinberg added that the effect carries over even to lower-stakes settings like smelling wine, where the specific notes that might suggest where the grapes were harvested only follow after we get past the immediately overwhelming impression of alcohol.

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There are no immediate therapeutic applications of the research, Rinberg said. But a better understanding of how the brain perceives scent could one day shed more light on other scientific questions that also involve smell, such as why people sometimes temporarily lose their sense of smell when sick, which has been observed in some patients with Covid-19. Verhagen said research on the logic of the olfactory system could also be of use in developing new technologies.

“In terms of medicine, there is increased interest in brain-machine interfaces. And so it is very important to understand how the brain encodes stimuli,” he said. “If we understand that coding logic, we can use that to help people who have deficits.”

About the AuthorReprints
Juliet Isselbacher
Juliet Isselbacher is a STAT intern jointly supported by the Institute of Politics and the Global Health Institute at Harvard, where she is a rising junior. She is studying philosophy and has keen interests in the evolution of epistemology and the history of science. Juliet also reports for The Harvard Crimson, where she has written about the faculty’s scientific innovations, the intersection of art and medicine, and the ways in which coronavirus reconfigured campus life. Her dog is named Darwin, after the biologist.