How fruit flies sniff out their surroundings

Fruit flies – Drosophila melanogaster – have a complicated relationship with carbon dioxide. In some contexts, CO₂ indicates palatable food sources, since sugar-fermenting yeasts in fruit produce the molecule as a by-product. But in other cases CO₂ can be a warning to stay away, indicating a low-oxygen or crowded environment with too many other flies. How do flies tell the difference?

Now, a new study shows that fruit fly olfactory neurons — the ones responsible for sensing chemical “smells” like CO₂– have the ability to talk to each other in a previously undiscovered way. The work provides insight into the fundamental processes by which brain cells communicate with each other, and also provides new clues to solving the long-standing mysteries surrounding fruit flies and CO₂.

The research was conducted in the lab of Elizabeth Hong (BS ’02), Assistant Professor of Neuroscience and Chen Fellow of the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. An article describing the study appears in the journal Current Biology on 6.9.

“KO₂ is an important but complex signal that occurs in all sorts of situations in the natural environment, and it illustrates a key challenge neurobiologists face in understanding the brain: how does the brain process the same sensory signal in different contexts so that the animal can use it appropriately can react?” says Hong. “We are tackling this question with the fly’s olfactory system, one of the best-studied and best-characterized sensory circuits. And yet, with this research, we discovered a surprising new phenomenon in how the brain processes sensory signals.”

The sense of smell or the sense of smell was the original sensory system that evolved in all animals. Although humans are primarily visual, most animals use smell as the primary way to understand their surroundings: sniffing out food, avoiding predators, and finding mates. Fruit flies are a particularly handy model for understanding the biological mechanisms underlying the sense of smell: a fruit fly has only around 50 different olfactory receptors, a human around 400 to 500 and a mouse more than a thousand.

A fly’s “nose” are its two antennae. These antennae are covered with thin hairs called sensilla, and inside each sensillum are the olfactory neurons. Smells – like CO₂ or the volatile esters produced by rotting fruit – diffuse into tiny pores on the sensilla and bind to corresponding receptors on the olfactory neurons. Neurons then send signals through the sensillum and into the brain. Although we don’t have antennae, an analogous process happens in your own nose when you lean forward to sniff a whiff of delicious food or shy away from bad smells.

While most odors activate about 20 different types of sensory neurons simultaneously in fruit flies, CO₂ is unusual in that it only activates a single type. Using a combination of genetic analysis and functional imaging, researchers at the Hong lab discovered that the exit cords, or axons, of the CO₂-Sensitive olfactory neurons can actually talk to other olfactory neural channels — particularly the neurons that recognize esters, molecules that smell particularly delicious to a fruit fly.

However, this olfactory crosstalk depends on the timing of CO₂ Hints. If CO₂ is detected in fluctuating pulses, e.g. B. a windborne cue from a distant food source, the CO₂-Sensing olfactory channel sends a message to the channels that encode esters, signaling the brain that delicious food is on the wind. However, if CO₂ in the local environment is continuously increased, for example by a rotting tree trunk, this crosstalk is quickly shut down and the CO₂-sensitive neurons directly signal the brain to avoid the source.

This is the first time that olfactory neurons have been shown to communicate with each other between their axons, processing incoming information before those signals ever reach the brain. The results contradict the prevailing dogma in neuroscience that information processing is limited to the integration of inputs by neurons; The new findings show that signals are also reformatted on the output side.

The scientists also discovered how flies behave towards CO₂ also depends on the timing of CO₂ signals. “We found that the behavior of the animal is influenced by the temporal structure of the CO₂ signals,” says Hong. “When the fly steps into a cloud with increased CO₂, it tends to deviate from the direction of travel. But in an environment where CO₂ pulsates, the fly will run upwind towards the source of the odor. This difference in the behavior of flies to fluctuating CO₂versus persistent CO₂corresponds to the dependency of the crosstalk on the CO₂-sensing neurons to attraction-promoting food-sensing neurons.”

Understand the olfactory sense of fruit flies, particularly with regard to the perception of CO₂, is a longstanding goal for Caltech researchers. Decades ago, researchers in the lab of David Anderson – Seymour Benzer, professor of biology; Tianqiao and Chrissy Chen Institute for Neuroscience Leadership Chair; Investigator, Howard Hughes Medical Institute; Director, Tianqiao and Chrissy Chen Institute for Neuroscience – discovered that flies avoid CO₂ as a chemical indicative of a crowded environment. But recently, researchers in Michael Dickinson’s lab – Esther M. and Abe M. Zarem Professors of Bioengineering and Aeronautics and Senior Biology and Bioengineering Officer – discovered that flies can also be attracted to CO₂when using it to sniff out a food source.

“Our work builds on these previous studies and offers a possible neural solution to how CO₂ could elicit contrasting behaviors in flies in different contexts. It was a highlight having my lab at Caltech, having the opportunity to interact directly with David’s and Michael’s labs and discussing the connections between our work and theirs,” says Hong.

The next big question is to understand how these parallel olfactory axons communicate with each other. The team ruled out most forms of classical chemical transmission that neurons use to communicate, and the mechanisms by which olfactory neurons can send and receive messages between their axons are mysterious. Solving this problem could provide new insights into how animal brains recognize and process sensory information.