Fruit flies, scientifically known as Drosophila melanogaster, have a surprisingly complex relationship with carbon dioxide (CO2). This common molecule can act as a dinner bell, signaling the presence of delicious, fermenting fruit. Yet, CO2 can also be a warning sign, indicating an environment that’s either low in oxygen or overcrowded with other flies. This raises a fascinating question: Do Flies Smell and, if so, how do they differentiate between these conflicting signals?
New research is shedding light on this very question, revealing that fruit fly olfactory neurons – the cells responsible for detecting airborne chemical “smells” like CO2 – possess an unexpected ability to communicate with each other. This newly discovered communication pathway offers valuable insights into the fundamental ways brain cells interact and provides crucial pieces to the puzzle of how fruit flies interpret CO2 in such nuanced ways.
The groundbreaking study was conducted in the laboratory of Elizabeth Hong, an assistant professor of neuroscience and Chen Scholar at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. Published in Current Biology, the research unveils a novel mechanism in the fly brain’s olfactory system.
“CO2 is a signal with multiple meanings in a fly’s world, appearing in many different contexts,” explains Professor Hong. “This complexity highlights a core challenge in neurobiology: How does the brain process the same sensory input differently depending on the situation, allowing for appropriate responses? We’re using the fruit fly olfactory system, a system we understand very well, to explore this question. And even within this well-studied system, we’re still uncovering surprising new ways the brain handles sensory information.”
Olfaction, or the sense of smell, is the most ancient sensory system, crucial for survival across the animal kingdom. While humans rely heavily on sight, smell remains the primary way most animals navigate their environment. From finding food and avoiding danger to locating mates, olfaction is key. Fruit flies are excellent models for studying the biological mechanisms of smell. With only about 50 types of odorant receptors, compared to hundreds in humans and over a thousand in mice, their system is simpler and more manageable to study.
Flies “smell” using their two antennae, which are covered in tiny hairs called sensilla. Inside each sensillum are olfactory neurons. When odors, like CO2 or the enticing scents from rotting fruit (esters), enter pores on the sensilla, they bind to specific receptors on these neurons. This binding triggers the neurons to send signals to the brain. Though we lack antennae, a similar process occurs in our noses when we inhale and detect scents.
Interestingly, while most smells activate around 20 types of sensory neurons in flies, CO2 uniquely activates only one type. Using advanced genetic analysis and functional imaging, Dr. Hong’s team made a remarkable discovery: the axons, or output cables, of these CO2-sensitive olfactory neurons can actually communicate with other olfactory channels. Specifically, they can talk to the neurons that detect esters, those molecules signaling delicious food to a fly.
However, this olfactory crosstalk is not constant; it depends on the pattern of CO2 detection. When CO2 is detected in pulses, like a whiff carried on the wind from a distant food source, the CO2-sensing channel signals to the ester-detecting channels. This combined message tells the fly’s brain that a food source is located upwind, enticing it to move towards the source. Conversely, if CO2 levels are consistently high in the immediate area, perhaps from fermenting material nearby, this crosstalk shuts down rapidly. In this case, the CO2-sensitive neurons signal directly to the brain to trigger avoidance behavior, telling the fly to get away.
This discovery marks the first time that olfactory neurons have been observed communicating with each other at the level of their axons, processing information before signals even reach the brain’s main processing centers. This finding challenges the traditional view in neuroscience that information processing primarily occurs through the integration of inputs by neurons. The new research shows that sensory signals are also refined and reshaped at the output stage.
Furthermore, the researchers found that fly behavior in response to CO2 is also dictated by the timing of the CO2 signal. “We observed that the temporal pattern of CO2 significantly impacts fly behavior,” Hong states. “When a fly encounters a cloud of constantly high CO2, it tends to turn away. But in an environment with pulsing CO2, the fly will move upwind, towards the odor source. This behavioral difference mirrors the way the crosstalk between CO2-sensing neurons and food-attraction neurons is modulated by the CO2 signal’s temporal structure.”
Understanding fruit fly olfaction, particularly their CO2 sensitivity, has been a long-term pursuit at Caltech. Decades ago, the lab of David Anderson discovered that flies avoid CO2 as an indicator of overcrowding. More recently, Michael Dickinson’s lab found that flies can also be attracted to CO2 when it signals a food source.
“Our research builds upon these earlier studies, offering a potential neural mechanism for how CO2 can trigger opposite behaviors in different situations,” says Hong. “Being at Caltech has provided a fantastic opportunity to engage with the labs of David and Michael, discussing how our work connects with theirs.”
The next major question for researchers is to unravel how these parallel olfactory axons communicate. The team has ruled out typical chemical neurotransmission, making the mechanism of this axonal communication a fascinating mystery. Solving this could provide new fundamental insights into how animal brains process and interpret sensory information from their world.
The research paper, titled “Parallel encoding of CO2 in attractive and aversive glomeruli by selective lateral signaling between olfactory afferents,” highlights Dhruv Zocchi as the first author. Funding for the study came from the National Science Foundation, the National Institutes of Health, and the Shurl and Kay Curci Foundation.
