Thousands of Different Scents – Scientists Solve a 30-Year-Old Mystery

It has been shown that worms can discriminate between various scents thanks to a chemical process.

The capacity to smell or not to smell might be the difference between life and death for soil-dwelling nematodes that rely largely on olfaction for survival. But for decades, researchers have been perplexed by how these worms can identify between more than a thousand different fragrances.

It has been shown that worms can discriminate between various scents thanks to a chemical process.

The capacity to smell or not to smell might be the difference between life and death for soil-dwelling nematodes that rely largely on olfaction for survival. But for decades, researchers have been perplexed by how these worms can identify between more than a thousand different fragrances.

The journal Proceedings of the National Academy of Sciences just published its findings.

After defending his thesis last week, Daniel Merritt, a first co-author on the article and a recent Ph.D. graduate from the van der Kooy group, had this to say: "The worms have an unbelievable sense of smell – it's really astounding."

They are capable of detecting a very broad range of substances, including chemicals emitted by soil, fruit, flowers, and bacteria. Even explosives and cancer indicators may be detected in patient urine, he claimed.

Due to their approximately 1300 odorant receptors, which were first discovered in C. elegans three decades ago, they are champion sniffers. Each receptor is dedicated to perceiving one sort of scent, just as in humans, who have roughly 400 receptors, but this is where the similarities end.

Hundreds of sensory neurons, each of which expresses a single receptor type, line the inside of our nostrils. A neuron's activation by an odorant sends a signal up its long process, or axon, further into the brain, where it is interpreted as smell. The physical separation of axonal wires delivering various scent impulses allows for smell discrimination.

However, the worms have only 32 olfactory neurons, which are home to all 1300 of their receptors.

The one neuron, one scent approach is obviously not going to work in this case, Merritt observed.

However, the worms are able to distinguish between several odors that are detected by the same neuron. Pioneering studies conducted in the early 1990s revealed that when worms are exposed to two scents, one of which is universally prevalent and the other is localized, they gravitate toward the latter. However, it is still unknown how this behavior is controlled at the molecular level.

The worm can apparently distinguish between the upstream components even though it appears that all the information this neuron senses is condensed into a single signal. We arrived at that conclusion, said Merritt.

Perhaps the worms are recognizing how potent the fragrances are, Merritt and former master's student Isabel MacKay-Clackett, who is also a co-first author on the article, hypothesized.

They reason that since odors are all around, the worms would eventually grow desensitized to them and ignore them since they are not the most reliable indications. The remaining odors, which may be more helpful in influencing behavior, would then be able to activate their receptors and result in signal transduction.

Additionally, they had a hunch on the molecular mechanics of this. A well-known desensitizer of the so-called G protein-coupled receptors (GPCRs), a wide family of proteins that are sensitive to external stimuli and to which odorant receptors belong, is a protein known as arrestin. For instance, arrestins enable humans to modify vision under intense light by reducing signaling across the retina's photon-sensing receptors.

When both smells are detected by the same neuron, the researchers wondered if arrestin may likewise function in worms to desensitize receptors for a stronger scent in favor of those for a weaker one. They subjected the arrestin-deficient worms to two different alluring scents in a Petri dish to verify their theory. The agar media was uniformly scented with one scent before the worms were added on top. The other odor was concentrated in a single area away from the worms.

The worms lost their ability to locate the source of the weaker scent without arrestin. According to MacKay-Clackett, arrestin works similarly to the human eye squinting in bright sunlight by taking away an overwhelming sense—in this case, ambient scent—so that the worms can detect a specific fragrance and go towards it.

Arrestin is not necessary, though, when the odors are detected by several neurons, indicating that worms use the same method of discernment as vertebrates when the smell signals are sent through various axons.

According to Merritt, the researchers examined several combinations of scents and neurons and discovered they all followed the same rules. Additionally, they discovered that arrestin blocking medications eliminated scent discrimination.

The discovery is important because it provides the first concrete proof that arrestin may fine-tune a variety of feelings.

According to Merritt, there has never been a known instance in biology where arrestin has been employed to allow for the differentiation of signals coming from outside the cell.

When many GPCRs are expressed on the same cell, particularly in the brain, he continued, the same process could also be at work in other species. There is a chance that arrestin, of which there are four varieties in humans, might be crucial for information processing. Our brains are soaked in neurochemicals that communicate through hundreds of distinct GPCRs.

The incredible ability of worms to smell is explained in part by our research, but it also advances our knowledge of how GPCR signaling functions more generally in animals, according to Merritt.