Derek van der Kooy, a professor of molecular genes at the Temerty Faculty of Medicine, University of Toronto, and director of the Donnelly Centre for Cellular and Biomolecular Research, acted as the studys lead researcher. The worm Caenorhabditis elegans is among the design organisms used in the neuroscience studies performed at the van der Kooy laboratory.
The head of an adult C. elegans worm. An olfactory nerve cell revealing a particular kind of odorant receptor is shown in green. Credit: Daniel Merritt
Their results were recently published in the journal Proceedings of the National Academy of Sciences.
” The worms have an incredible sense of odor– its absolutely remarkable,” says Daniel Merritt, a very first co-author on the paper and a recently minted Ph.D. graduate from the van der Kooy laboratory following his thesis defense recently.
” They can find an extremely variety of compounds, such as molecules launched from soil, fruit, flowers, germs. They can even smell dynamites and cancer biomarkers in the urine of patients,” he said.
C. elegans are champion sniffers thanks to having around 1300 odorant receptors, whose discovery began three years earlier. Like in people, who have about 400 receptors, each receptor is devoted to picking up one kind of odor, however this is where similarities end.
Our noses are lined with numerous sensory neurons, each expressing just one receptor type. When an odorant triggers an offered nerve cell, the signal travels much deeper into the brain along its long procedure, or axon, where it is perceived as smell. Odor discrimination is enabled by the physical separation of axonal cable televisions bring various odor signals.
The worms, however, have just 32 olfactory neurons, which hold all of their 1300 receptors.
” Clearly, the one neuron-one odor strategy is not going to work here,” Merritt said.
Yet, the worms can discriminate between different smells sensed by the very same nerve cell. Pioneering research from the early 1990s showed that when exposed to 2 appealing smells, where one is consistently present and the other is localized, the worms crawl towards the latter. However how this behavior is controlled at the molecular level stayed unclear.
” It seems that all the information that is noticed by this nerve cell gets compressed into one signal, and yet the worm can in some way inform the difference between the upstream parts. Thats where we concerned it,” said Merritt.
Merritt and previous masters trainee Isabel MacKay-Clackett, likewise a co-first author on the paper, reasoned that possibly the worms are noticing how strong the smells are.
According to their hypothesis, the smells that are everywhere are not the most useful cues and would become desensitized in some method, implying the worms would neglect them. This would leave the weakly present smells, which may be more useful in assisting behavior, able to trigger their receptors and cause signal transduction.
They also had a hunch about how this could work at the molecular level. A protein called arrestin is a well-established desensitizer of the so-called- G protein-coupled receptors (GPCRs), a big family of proteins that perceive external stimuli, to which odorant receptors belong to. Arrestins for example allow us to adjust vision in intense light by damping down signaling through the photon-sensing receptors in the retina.
The team questioned if arrestin might likewise act in worms to desensitize receptors for a more powerful odor in favor of those for a weaker one when both are sensed by the same nerve cell. To evaluate their hypothesis, they exposed the worms doing not have the arrestin gene to 2 various appealing smells in a Petri meal. They mixed one odor into the agar medium to make it consistent and put the worms on top. The other smell was put at one spot some distance from the worms.
Without arrestin, the worms were no longer able to find the source of the weaker odor. Like in the human eye squinting in bright sunshine, arrestin helps remove an overpowering experience– ambient odor in this case– so that the worms can move and notice a localized smell towards it, MacKay-Clackett said.
Arrestin is not needed, however, when the smells are sensed by different neurons, suggesting that the worms use the same discrimination strategy as the vertebrates when the smell signals travel down different axons.
The group took a look at different sets of smells and nerve cells and found they all followed the very same reasoning, said Merritt. They likewise used drugs to block arrestin and found that this too eliminated odor discrimination.
Since it is the first evidence revealing that arrestin can fine-tune several feelings, the finding is substantial.
” There is no case known in biology prior to this where arrestin is being used to enable discrimination of signals external to the cell,” said Merritt.
He added that the very same mechanism might be playing out in other animals when numerous GPCRs are revealed on the same cell, particularly in the brain. Our brains are bathed in neurochemicals that signal through numerous various GPCRs, raising a possibility that arrestin, of which there are 4 enters people, might be crucial for details processing.
” Our work supplies one piece of the puzzle of how the worms fantastic sense of odor works, but it also informs our understanding of how GPCR signaling works more broadly within animals,” said Merritt.
Reference: “Arrestin-mediated desensitization allows intraneuronal olfactory discrimination in Caenorhabditis elegans” by Daniel M. Merritt, Isabel MacKay-Clackett, Sylvia M. T. Almeida, Celina Tran, Safa Ansar and Derek van der Kooy, 25 July 2022, Proceedings of the National Academy of Sciences.DOI: 10.1073/ pnas.2116957119.
Smell discrimination is enabled by the physical separation of axonal cables carrying different odor signals.
The worms can discriminate in between different smells sensed by the same nerve cell. The team wondered if arrestin may also act in worms to desensitize receptors for a more powerful odor in favor of those for a weaker one when both are picked up by the exact same nerve cell. To evaluate their hypothesis, they exposed the worms lacking the arrestin gene to two various attractive smells in a Petri dish. They mixed one odor into the agar medium to make it uniform and put the worms on top.
Unlike human beings, the nematode Caenorhabditis elegans has just 32 olfactory nerve cells, which hold all of their 1300 receptors.
A molecular system that allows worms to identify different smells has been found.
For soil-dwelling nematodes that depend mostly on olfaction for survival, the ability to smell or not to smell might be the distinction in between life and death. Nevertheless, scientists have actually been baffled by how these worms compare more than a thousand unique scents for decades.
Researchers from the University of Toronto have now identified the molecular mechanism behind this procedure and have revealed that it consists of a conserved protein that aids in the equilibration of human eyesight. Their discovery has repercussions that go beyond nematode olfaction and may even shed light on how human brains operate.
