Rethinking Scents: Are Lab Experiments Overpowering the Nose?
By Archyde News Journalist
For years, olfactory neuroscientists have quietly acknowledged a essential issue: their experimental methods often involve bombarding lab animals wiht unnaturally strong odors. These concentrated blasts, delivered in short bursts, may not accurately replicate the complex, subtle scent landscapes animals navigate in the real world.
As Sandeep Robert Datta, professor of neurobiology at Harvard University, points out, the typical lab setup “likely bears little resemblance—either in concentration or in form—to the ways in which animals naturalistically interact with odors.” In their natural habitats, animals encounter a symphony of faint, interwoven scents carried on the breeze.
The challenge, according to David Coppola, retired professor of biology at Randolph-Macon College, has been the difficulty in measuring odors in natural settings. “We have our hands tied behind our back because it’s very challenging to measure odors in natural settings,” Coppola explains. This lack of real-world data has forced researchers to rely on simplified, often exaggerated, odor stimuli in their experiments.
Now, a groundbreaking effort is shedding light on this discrepancy, possibly reshaping how we study the sense of smell.
Aromatic Inventory: charting the Natural Odor Landscape
Driven by the need for more ecologically relevant data, Elizabeth Hong, professor of neuroscience at the California Institute of Technology, and Matt Wachowiak, professor of neurobiology at the University of Utah, embarked on an ambitious project: to compile a complete database of natural odorant concentrations.
Their inquiry spanned diverse fields, from food science to environmental toxicology, meticulously gathering data on odorant levels in various environments. These included a fragrant pine forest, a pungent pig farm, a composting bioreactor, and even a cannabis grow room. much of their data came from “headspace” studies,which measure odorants emanating from fragrant items enclosed in a jar.
The findings, detailed in their paper published March 5 in The Journal of Neuroscience, revealed a stark contrast: Natural odor concentrations typically fall in the parts-per-billion (ppb) range, while olfactory experiments frequently enough use concentrations in the parts-per-million (ppm) range. To put this in outlook, the difference in scale is like comparing a single drop of water in a 10-gallon fish tank to that same drop in a 10,000-gallon swimming pool.
This gap raises critical questions about the validity of extrapolating lab findings to real-world scenarios. “We are learning about the sense of smell from a relatively unphysiological experimental setting,” notes Marc Spehr, professor of chemosensation at RWTH Aachen University, who was not involved in the study. He likens the current approach to audition researchers studying the auditory system “by putting your subjects next to a jet plane.”
The Implications for Olfactory Research
While acknowledging the significant insights gained from studies using strong stimuli, Hong emphasizes the need to account for odor complexity and concentration to address more nuanced questions.”Studies that use strong stimuli have gleaned important insights about the olfactory system,” Hong says. “But as different concentrations of odors activate olfactory brain areas in different ways, it’s time to take the complexity and concentration of odors into account to answer more nuanced and mechanistic questions.”
Spehr echoes this sentiment, stating, “For the evolution of the field, this will be critically important.”
Imagine trying to understand the complexities of human vision by only showing subjects extremely radiant flashing lights.While you might learn something about the basic functions of the eye,you would miss crucial details about how we perceive subtle differences in color,contrast,and depth in everyday scenes. Similarly, using overly strong odors might potentially be masking the nuances of how the olfactory system operates under normal conditions.
How Smell Works: A Primer
An animal’s sense of smell begins when odor molecules bind to receptors on neurons in the nasal epithelium. These neurons then connect with neurons in the olfactory bulb, forming clusters of synapses called glomeruli. Each glomerulus receives input from a single receptor type. As multiple odorants can bind to each receptor, and each odorant can bind to multiple receptors with varying affinities, the brain decodes an odor’s identity from its unique pattern of activated glomeruli – or so the prevailing hypothesis suggests.
However, subtle scents behave differently. Wachowiak reported in 2022 that at low concentrations (in the ppb range), about 25 percent of glomeruli respond to only one odorant apiece. This concentration level aligns with the environmental concentrations cataloged by Wachowiak and Hong and falls within the range that rodents can detect in tests.
Often, then, “the olfactory system is functioning at a near-threshold level,” Wachowiak proposes. “That’s changed the way I think about the question of, ‘what’s the olfactory system doing for the animal, and how is it being used?’” the data compiled in the review suggest the “most common operating regime of the system is just trying to detect an odor in the first place,” he says.
Datta presents a contrasting viewpoint, acknowledging that experimental concentrations are likely too high and that mice can detect very low concentrations. However, he questions whether this near-threshold detection is the system’s primary function in the wild. “But that’s not the same as arguing that in the natural world, under most biological circumstances, that’s what the system is doing,” datta says.
Datta’s research suggests a different model. Olfactory sensory neurons in the nose express activity-dependent genes that change based on the scents an animal encounters and the duration of exposure. In a 2021 paper, datta accurately predicted which of three differently scented cages a mouse had occupied based on its olfactory sensory neuron transcriptome. “What it means is that, under normal circumstances, your nose is always contending with enough odor to activate every channel differentially,” Datta explains. “So instead of living in a world where odors are fundamentally sparse, our data argue that you live in a world where odors are fundamentally dense” and distracting.”
Furthermore, datta notes that some environments, such as a mouse burrow, likely contain high concentrations of certain odors. he concludes that the olfactory system “is capable of all sorts of things and probably deals with dense and sparse all at onc, all the time.” Nonetheless, he emphasizes the importance of being aware of the concentrations used in experiments and how they reflect real-world conditions.
The Technical Hurdles of Measuring Odors
A major factor contributing to this methodological challenge is the inherent difficulty in measuring odorant concentrations in vapor form. “I won’t call it a nightmare, but close to it,” Spehr says.
Measuring auditory or visual stimuli is far simpler. Wachowiak notes that you can easily measure light and sound intensity with a smartphone app.Though, accurately measuring odor intensity requires “very expensive, sophisticated” chemical equipment.
Moreover, odorants travel in plumes, creating pockets of varying concentrations. Standard measurement methods struggle to capture this dynamic variance. Even with rough concentration measurements, it’s challenging to determine the exact concentration an animal inhales as it moves, according to Tobias Ackels, group leader at the university of Bonn, who was not involved in the study.
Consequently, researchers often fail to report their stimuli in sufficient detail to determine precise odorant concentrations. Hong and Wachowiak’s review found this to be the case in about one-third of rodent studies and 80 percent of insect studies.They propose a feasible initial step: Researchers can use the vapor pressure of an odor to estimate its approximate concentration.
“It’s really not very precise,” Spehr says of that approach, “but it’s something that gives you a ballpark data of what could be the concentration in the air.”
Another option is to use natural odor sources rather of single-molecule odors from chemical companies. While suitable for research questions agnostic to odorant identity, this approach is less effective for questions about “dose dependence, molecular feature detection and similar things,” Spehr says.
Researchers can also create blends of single-molecule odors that mimic natural odor sources, hong suggests. “These types of stimuli will complement one another.”
Moving Forward: Towards More Realistic Olfactory Research
Coppola, who was not involved in creating the concentration database, calls it a “heroic effort.” However, he believes that the compiled settings and headspace studies are not sufficient replacements for measurements taken directly from animals’ natural environments, such as mouse burrows. “We need to go out in the field, where these behaviors are actually happening, and measure some concentrations of important molecules,” he says.
Simultaneously occurring, Ackels suggests that the database is a valuable starting point for researchers aiming to calibrate their concentrations to more appropriate levels.
Datta concludes that the review is “super critically important.” “I think we do need to change our perspective, to think more about the naturalistic function of olfaction.”
| Odorant Origin | Typical Concentration | Experimental Concentration | Relevance to U.S.Context |
|---|---|---|---|
| Pine Forest | Parts per billion (ppb) | Parts per million (ppm) | Critically important for understanding forest ecology and wildlife behavior in U.S. national parks and forests. |
| Pig Farm | Parts per billion (ppb) | Parts per million (ppm) | Relevant to agricultural practices and environmental regulations in states with large livestock industries like Iowa and North Carolina. |
| Cannabis Grow Room | Parts per billion (ppb) | Parts per million (ppm) | increasingly important as cannabis legalization spreads across the U.S., impacting odor control and public health policies. |
The implications of this research extend beyond academic labs. Understanding natural odor landscapes could have practical applications in areas like:
- Pest Control: Developing more effective and targeted pest control strategies by understanding the subtle scents that attract or repel pests.
- Environmental Monitoring: Using scent profiles to detect pollutants or monitor ecosystem health.
- Product Development: Creating more appealing and effective fragrances and flavors for consumer products by mimicking natural scent combinations.
Given the complex nature of scent perception, how do you think researchers can best balance the need for controlled experiments with the demand of real-world accuracy in their olfaction studies? Share your thoughts in the comments below!
Rethinking Scents: An Interview with dr. Elizabeth Hong on Natural odor Landscapes
By Archyde News Journalist
Interview with dr. Elizabeth Hong
Welcome, Dr. Hong, and thank you for joining us today. Your recent research on the disparity between lab-created odors and those found in nature is engaging. Can you give us a brief overview of the main findings?
Dr. Hong: Thank you for having me.The core of our work, published in The Journal of Neuroscience, highlights a significant difference: laboratory experiments often use odor concentrations in the parts-per-million (ppm) range, while natural environments, like a pine forest or a pig farm, typically present odors in the parts-per-billion (ppb) range. This gap suggests we might be missing crucial aspects of how animals, and by extension, we, perceive and interact with scents.
The aromatic Inventory: Digging Deeper
That’s a striking difference, akin to comparing a drop of water in a fish tank to a drop in a swimming pool, as the paper described. Your team meticulously compiled data from diverse environments. What motivated you to embark on such an ambitious project?
Dr. Hong: We realized a critical lack of data. Many studies, while insightful, frequently enough don’t reflect the complexity of natural scentscapes. The need for more ecologically relevant data drove us to create a extensive database of natural odorant concentrations. We wanted a baseline to understand what animals actually experience in their daily lives regarding the sense of smell.
Implications of the Research
The implications are pretty broad, aren’t they? How might these findings reshape the way we approach olfactory research moving forward?
Dr. Hong: we hope this encourages researchers to consider both the complexity and concentration of odors. While strong stimuli provide valuable insights, understanding the nuances of scent perception demands a shift towards more realistic experimental settings. This means accounting for the potential differences in how different odor concentrations activate the brain.
Overcoming Technical Hurdles
The article mentions the inherent difficulties in measuring odorant concentrations. What are some of the biggest technical hurdles, and how can researchers overcome them?
Dr.hong: Measuring odors in vapor form is, as Professor spehr put it, “close to a nightmare.” Compared to the ease of measuring light or sound, we need sophisticated and expensive equipment. the dynamic variance of odor plumes, with pockets of varying concentration, adds further complexity. A practical initial step could be using the vapor pressure of an odorant to estimate concentration, or better yet, using natural odor sources and creating blends that mimic them.
Applications Beyond the Lab
Beyond the academic sphere, what are the potential real-world applications of this kind of research?
Dr. Hong: The possibilities are quite exciting. We could develop more effective pest control strategies, by understanding the subtle scents that attract or repel pests. We can enhance environmental monitoring, by using scent profiles to detect pollutants or track ecosystem health. Product developers can also benefit, by creating more appealing and effective fragrances and flavors that mimic natural scent combinations, and are applicable to the U.S.Context.
The Future of Olfactory research
This is truly groundbreaking work, Dr. Hong. Where do you see the field of olfactory research heading in the next few years?
Dr. Hong: I believe we’ll see a greater focus on the naturalistic function of olfaction. There’ll be more field studies to understand how animals interact with scents and a push to create more ecologically valid experimental designs. It is an exciting time to be studying the sense of smell and how animals use it to navigate their surroundings, especially with potential applications in many different areas, from pest control to creating fragrances.
Discussion Question
Given the complex nature of scent perception, how do you think researchers can best balance the need for controlled experiments with the demand of real-world accuracy in their olfaction studies? Share your thoughts in the comments below!
