Science Decodes How the Brain Senses Smell

Scientists have further decoded how mammalian brains perceive odors and distinguish one smell from thousands of others.

With loss of smell, one of the earliest signs of COVID-19, it’s especially timely that researchers have decoded more how we use our sense of smell.

In experiments in mice, NYU Grossman School of Medicine researchers have for the first time created an electrical signature that is perceived as an odor in the brain's smell-processing center, the olfactory bulb, even though the odor does not exist. Funding support for the study was provided by National Institutes of Health.

Because the odor-simulating signal was human-made, researchers could manipulate the timing and order of related nerve signaling and identify which changes were most important to the ability of mice to accurately identify the "synthetic smell."

"Decoding how the brain tells apart odors is complicated, in part, because unlike with other senses such as vision, we do not yet know the most important aspects of individual smells," says study lead investigator Edmund Chong, MS, a doctoral student at NYU Langone Health. "In facial recognition, for example, the brain can recognize people based on visual cues, such as the eyes, even without seeing someone's nose and ears," says Chong. "But these distinguishing features, as recorded by the brain, have yet to be found for each smell."

The current study results, published online in the journal Science on June 18, center on the olfactory bulb, which is behind the nose in animals and humans. Past studies have shown that airborne molecules linked to scents trigger receptor cells lining the nose to send electric signals to nerve-ending bundles in the bulb called glomeruli, and then to brain cells (neurons).

The timing and order of glomeruli activation is known to be unique to each smell, researchers say, with signals then transmitted to the brain's cortex, which controls how an animal perceives, reacts to, and remembers a smell. But because scents can vary over time and mingle with others, scientists have until now struggled to precisely track a single smell signature across several types of neurons.

For the new study, the researchers designed experiments based on the availability of mice genetically engineered by another lab so that their brain cells could be activated by shining light on them -- a technique called optogenetics. Next they trained the mice to recognize a signal generated by light activation of six glomeruli -- known to resemble a pattern evoked by an odor -- by giving them a water reward only when they perceived the correct "odor" and pushed a lever.

If mice pushed the lever after activation of a different set of glomeruli (simulation of a different odor), they received no water. Using this model, the researchers changed the timing and mix of activated glomeruli, noting how each change impacted a mouse's perception as reflected in a behavior: the accuracy with which it acted on the synthetic odor signal to get the reward.

Specifically, researchers found that changing which of the glomeruli within each odor-defining set were activated first led to as much as a 30 percent drop in the ability of a mouse to correctly sense an odor signal and obtain water. Changes in the last glomeruli in each set came with as little as a 5 percent decrease in accurate odor sensing.

The timing of the glomeruli activations worked together "like the notes in a melody," say the researchers, with delays or interruptions in the early "notes" degrading accuracy. Tight control in their model over when, how many, and which receptors and glomeruli were activated in the mice, enabled the team to sift through many variables and identify which odor features stood out.

"Now that we have a model for breaking down the timing and order of glomeruli activation, we can examine the minimum number and kind of receptors needed by the olfactory bulb to identify a particular smell," says study senior investigator and neurobiologist Dmitry Rinberg, PhD.

The first tell is the loss of smell

Earlier this month, researchers from the University of California in San Diego released a study indicating that sensory loss, including the sense of smell, was strongly associated with COVID-19.

Dr. Carol H. Yan, an otolaryngologist at UC San Diego Health, said the research suggests that if you have smell and taste loss, you’re 10 times more likely to have COVID-19.

“This study supports the need to be aware of smell and taste loss as early signs of COVID-19,” Yan said in the study’ release.

According to doctors interviewed by Healthline, it’s important for patients and doctors alike to be aware of this connection, even if the data is preliminary.

“From what we’ve seen, as many as two-thirds of those with COVID-19 may experience a temporary loss or distortion of their smell, as well as taste,” Dr. Robert Quigley, a senior vice president and regional medical director of International SOS, told Healthline.

A study published in early May reported that people who experience a loss of smell tend to have milder cases of COVID-19.

Typically, one to two percent of North Americans report problems with their sense of smell. Problems with the sense of smell increase as people get older, and they are more common in men than women. In one study, nearly one-quarter of men ages 60–69 had a smell disorder, while about 11 percent of women in that age range reported a problem.

But that doesn’t mean people don’t have powerful smell potential. A 2014 study showed that we can distinguish at least 1 trillion different odors — up from previous estimates of a mere 10,000.

In fact, some facts about smell often surprise people. For instance, scent cells are actually renewed in the body every 30 to 60 days. People can smell fear and disgust and smell is the oldest sense. Finally, the one fact about smell that men and women fully realize is that women have a better sense of smell than men.

Study Conclusions

Senior investigator and neurobiologist Dmitry Rinberg, PhD., an associate professor at NYU Langone and its Neuroscience Institute, says the human nose is known to have some 350 different kinds of odor receptors, while mice, whose sense of smell is far more specialized, have more than 1,200.

"Our results identify for the first time a code for how the brain converts sensory information into perception of something, in this case an odor," adds Rinberg. "This puts us closer to answering the longstanding question in our field of how the brain extracts sensory information to evoke behavior."