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

The nematode Caenorhabditis elegans, in contrast to humans, has only 32 olfactory neurons, which are home to all 1300 of its receptors.

It has been found that worms can distinguish between various scents thanks to a chemical process.

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

In order to help with the equilibration of human eyesight, a conserved protein has been shown to be involved in this process' molecular mechanism by University of Toronto researchers. Beyond nematode olfaction, this study has ramifications that could potentially provide insight into how human brains work.

The study's principal investigator was Derek van der Kooy, a professor of molecular genetics at the Temerty Faculty of Medicine, University of Toronto, and the head of the Donnelly Centre for Cellular and Biomolecular Research. One of the model species employed in the van der Kooy lab's neuroscience research is the worm Caenorhabditis elegans.

a mature C. elegans worm's head. Green represents an olfactory neuron that expresses a specific kind of odorant receptor. Daniel Merritt is to thank

The journal Proceedings of the National Academy of Sciences recently 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 biomarkers can 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 sensing one type of smell, just like 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 noses. A neuron's activation by an odorant sends a signal up its long process, or axon, deeper 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 smell approach is obviously not going to work in this case, Merritt observed.

However, the worms are able to distinguish between various 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 sensing 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 become desensitized to them and ignore them because 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 us 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 act in worms to desensitize receptors for a stronger smell 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 smell 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 smell—so that the worms can detect a specific fragrance and go towards it.

Arrestin is not necessary, though, when the odors are detected by various neurons, indicating that worms use the same method of discernment as vertebrates when the smell signals are transmitted 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 smell 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 used 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 might also be at work in other animals. There is a chance that arrestin, of which there are four varieties in humans, could 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.                                                                                                                                                                                                                             By UNIVERSITY OF TORONTO