Fast-changing smells help mice learn about their surroundings

May 18, 2021

Mice can get information about their environment by detecting subtle changes in odors. (AP Photo/Patrick Semansky)

By detecting subtle but rapid changes in odors moving through the air, mice are able to gather information about the space around them while also overcoming behavioral challenges, such as distinguishing sources of odor, new research suggests.

The findings, published May 5 in Nature, alter current thinking on the way mammals detect and process odors, suggesting that they are much more sensitive to minute changes in smell than previously considered.

"The fact that we are not aware of smells changing quickly doesn't necessarily mean that we are not using this kind of information to actually make sense of the general environment around us," said senior author Andreas Schaefer, a neuroscience professor at University College London. Schaefer is also the leader of a lab at the Francis Crick Institute, which conducted the research.

Parsing out different odors is a classic example of a cocktail-party problem, a frequent occurrence in which an organism must distinguish between a host of related stimuli, like trying to hear one person at a party. While there are many examples of animals solving this problem for auditory stimuli, smells make for a more complex party.

"In the olfactory system, we have that problem maybe even more profoundly because every odor source is hundreds of different types of molecules," Schaefer said. "And then you have hundreds of different sources in the environment, so before you actually want to figure out what's out there, you need to figure out which chemicals belong to what."

In addition to having a complex composition, odors are also difficult to differentiate and identify because they move through the air in turbulent plumes emanating from the source, rather than simply diffusing into the surrounding environment. This causes rapid fluctuations in concentration over time.

Research has suggested for decades that these concentration fluctuations could contain rich information for animals about the location and composition of an odor source. However, this hypothesis has proved difficult to confirm, causing most neuroscientists to dismiss it.

But Schaefer and his team refused to give up on the problem, taking decades to work out a way to mimic the rapid fluctuations of odor found in nature.

"We had to develop devices that allowed us to deliver these millisecond-precise pulses so we can study it properly," Schaefer said. "That's why it took, on and off, 20 years to get to that point where we could present these stimuli, could measure how mice were able to react to these fast-modulating stimuli."

After using computer modeling to decide whether the experiment was feasible, to which they got a "resounding yes," as Schaefer put it, the researchers tested the effect of different timings of these pulses on the brains of mice by imaging the brain directly. They also put the mice through a series of behavioral tests in a large, enclosed system that the researchers termed the AutonoMouse system, which Schaefer had developed in a previous study.

According to Schaefer, this type of system "allows the animals to live in a low-stress environment where they happily do experiments continuously during night without humans interfering with them."

The mice were trained to lick a small tube if they experienced two simultaneous odors, but not to lick it if they experienced two odors at different times. Correct responses were rewarded with a drink of water, and incorrect ones were punished by a brief break before the next trial. And because the AutonoMouse system is self-contained and self-initiated, the mice did most of the work, allowing the researchers to gather data for many more trials than would have been possible with other methods.

By starting with the two distinct odors farther apart, representing a lower-frequency odor plume, and then working their way toward higher frequencies, the researchers were able to determine at what frequency the two separate smells started blending into one for the mice.

The team found the answer to be 40 hertz, meaning the mice can distinguish 40 distinct smell states in a single second. And while Schaefer said that he isn't very surprised by this finding because it was supported by prior hypotheses, he explained that his team's initial data was "very surprising" to other researchers in the field when first presented, because they didn't even know a study like this was possible.

The next steps for the team will be figuring out how to apply its odor-delivery system toward gathering much more nuanced data on the brain itself, because the current study focused largely on behavior. The team is also excited for the possibilities of using the system to study the entire mammalian class.

"The brilliant thing is now we have this really complex set of fluctuating stimuli, where there's information about space, about where things are, about where they're moving, etc.," Schaefer said. "We don't know how we can extract information from that, but it's very likely that it's possible that we can figure out generally how the mammalian brain processes information, but in a very mechanistic way."

The study, "Fast odour dynamics are encoded in the olfactory system and guide behaviour," published May 5 in Nature, was authored by Tobias Ackels, Andrew Erskine, Debanjan Dasgupta, Sina Tootoonian, Julia J. Harris and Andreas T. Schaefer, Francis Crick Institute and University College London; and Alina Cristina Marin, Tom P. A. Warner and Izumi Fukunaga, Francis Crick Institute.

Correction: A previous version of this story misspelled the name of the Francis Crick Institute. The error has been corrected.

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