A Nose For Noxious Substances

Using transgenic zebrafish, scientists in Japan have discovered a neural pathway that controls behavioral responses to carbon dioxide.

AsianScientist (Feb. 12, 2018) – Scientists in Japan have discovered a neuronal pathway that allows zebrafish to detect and avoid carbon dioxide. Their work is published in Cell Reports.

High levels of carbon dioxide are dangerous. Many animals have built-in avoidance behaviors that take over when necessary and people can even experience fear and panic attacks when too much carbon dioxide is in the air. Similarly, fish prefer to avoid swimming through a patch of carbon dioxide.

In efforts to understand the neurobiology behind these types of responses, a team of researchers at RIKEN in Japan used transgenic zebrafish to identify the signaling processes in the brain that enable avoidance of carbon dioxide. Zebrafish are useful because the behaviors of larvae are easy to characterize, and their transparent brains make imaging neuronal activity a breeze.

Larval zebrafish are known to have a fast response when touched on the head—they flee the threatening stimulus within 10 milliseconds.

“In contrast, we showed that their avoidance response to carbon dioxide happened after around four to five seconds, which is about 400 to 500 times slower,” said lead author Professor Tetsuya Koide of RIKEN.

Additionally, the escape routes taken by the fish to avoid carbon dioxide were much more variable than how they responded to being touched, and they swam away at much slower speeds. All these differences pointed to an as yet unknown sensation-response pathway in the brain.

To identify the responsible pathway, the researchers used transgenic zebrafish made specially for calcium imaging. This technique visualizes brain activity by genetically expressing fluorescent protein sensitive to calcium, a key molecule involved in the transmission of neuronal signals.

The team was able to see a series of responses to carbon dioxide in the brain, the earliest being in the olfactory bulb, the part of the brain that processes smell in mammals. A few seconds later, they saw responses in trigeminal sensory neurons, which carry touch and pain sensations from the face. The final response was from the habenula—a part of the brain known to be involved in learning associations with unpleasant experiences.

To determine which of these three systems was necessary for the response to carbon dioxide, the team used a laser to remove each one separately. They found that only damage to the trigeminal pathway and to the nose affected the response to carbon dioxide. This was somewhat surprising because damaging the olfactory pathway itself did not change the avoidance behavior.

“This meant that a non-olfactory component in the nose is critical for avoiding carbon dioxide,” Koide explained.

The team next wanted to determine how carbon dioxide was sensed in the nose. Calcium imaging of the zebrafish nose revealed a cluster of cells that responded to carbon dioxide. Tests indicated that these cells were part of the terminal nerve—also called cranial nerve zero—and their removal blocked the avoidance response to carbon dioxide. Thus, the zebrafish nose contains terminal nerve chemosensors that are unrelated to smell, and are instead involved in the control of behavioral responses to noxious chemicals.

“We were surprised to find that the terminal nerve acts as a carbon dioxide sensor in zebrafish,” said Koide. “Although it was identified as an additional cranial nerve in humans and other vertebrates more than a century ago, ours is the first to report its function in chemosensation.”

“As humans and other vertebrates also possess the terminal nerve system, we hope to further characterize its chemosensory functions across different species, including humans,” he added.

The article can be found at: Koide et al. (2018) Terminal Nerve GnRH3 Neurons Mediate Slow Avoidance of Carbon Dioxide in Larval Zebrafish.


Source: RIKEN; Photo: Shutterstock.
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