"It seems that C. elegans placed great value on the smell of salt, using a completely different circuit configuration in the brain to respond," says the lead researcher. "This may be because salt often represents bacteria, which are food for the worm"
It sounds like a party trick: Scientists can now look at the brain activity of a tiny worm and tell what chemical the animal smelled a few seconds ago. But the findings of a new study, led by Associate Professor Srikanth Chelasny of the Salk Institute, are more than a trick: They help researchers better understand how the brain works and integrates information.
"We found some unexpected things when we started looking at the effect of these sensory stimuli on individual cells and connections in the worm's brain," says Chelasny, a member of the Laboratory of Molecular Neurobiology and senior author of the new paper, published in the journal PLOS Computational Biology on November 9, 2021 .
Chelasny is interested in the way, at the cellular level, the brain processes information from the outside world. Researchers cannot simultaneously track the activity of each of the 86 billion brain cells in a living person - but they can in the microscopic worm Caenorhabditis elegans, which has only 302 neurons. Chelasny explains that in a simple animal like C. elegans, researchers can monitor individual neurons as they perform actions. Such a level of resolution is currently not possible in humans or even in mice.
Chelasny's team set out to test how C. elegans neurons respond to sniffing each of five different chemicals: benzaldehyde, diacetyl, isoamyl alcohol, 2-nonanone and sodium chloride (table salt). Previous studies have shown that C. elegans can distinguish between these substances, which to humans smell more or less like almonds, buttered popcorn, banana, cheese and salt. Researchers know how to identify the small handful of sensory neurons that directly sense these stimuli, but Chelasny's group was more interested in how the rest of the brain responded.
The researchers engineered C. elegans so that each of its 302 neurons contained a fluorescent sensor that lit up when the cell was active. They then watched through a microscope as they exposed 48 different worms to long bursts of five chemicals. On average, 50 or 60 neurons were activated in response to each chemical.
From looking at basic features of the data—such as how many cells were active at each point in time—Chelsany and his colleagues could not immediately distinguish between the different chemicals. So they turned to a mathematical approach called graph theory that analyzes the collective interactions between pairs of cells: When one cell is activated, how does the activity of other cells change in response?
This approach revealed that whenever C. elegans was exposed to sodium chloride (salt), there was first a burst of activity in one group of neurons - probably the sensory neurons - but then after about 30 seconds, trios of other neurons began to highly coordinate their activity. The same distinct triplets were not seen after the other stimuli, allowing the researchers to accurately identify - based only on the brain patterns - that the worm had been exposed to salt.
"It seems that C. elegans placed great value on the sound of salt, using a completely different circuit configuration in the brain to respond," says Chelasny. "This may be because salt often represents bacteria, which are food for the worm."
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