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The Sweet Taste of Fear

Science Sushi
By Christie Wilcox
Feb 23, 2012 11:00 PMNov 20, 2019 5:41 AM


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Lots of animals use chemical cues to avoid danger. Mice will run from the smell of cat urine, for example. But one particular instance of chemical fear signaling has been stumping scientists for 70 years; the release of Schreckstoff by schooling fish. For some species of fish, when a predator swoops in and injures one fish in a school, the rest will take off in fear. This much we know. In 1938, Austrian ethologist Karl von Frisch claimed that at the root of this behavior was a chemical alarm signal which he referred to as "Schreckstoff," which means "scary stuff" in German. Since von Frisch’s seminal work, over 100 published studies concerning Schreckstoff have demonstrated that certain fishes have some substance in their skin cells which is released when that fish is injured and causes other fish to scatter. That much, we know, too. This has perplexed scientists because it seems strange that any animal could evolve to give off that kind of chemical alarm. The other fish aren't fleeing from blood or any clear signals of death, so what are they so afraid of? And if it's not a signal of death but instead a signal of danger, as many scientists have argued, where is the benefit to the dying fish? You see, as much as we love the idea of altruism, it's not very common in the natural world - at least not in its pure form. Doing something purely for the sake of others is of little benefit to an individual from an evolutionary perspective. So, hypotheses have been thrown around wildly to explain this kind of altruistic signaling - perhaps the alarm is to protect close kin, or, somehow, the chemical actually attracts the would-be-predator's predators, thus giving the injured fish a chance to escape. Despite years of laboratory research, no hypothesis seems to be able to explain the presence of Schreckstoff. Furthermore, though some scientists have offered up potential compounds, what exactly Schreckstoff is has remained a mystery. Now, a team from Singapore has identified that the elusive Schreckstoff as the same compound that we take to improve our joints and treat osteoporosis: chondroitin sulfate.

Chondroitin sulfate is a specialized chain of sugars that is a major component of fish skin, just like it's a major component of our cartilage. Using zebrafish, a common laboratory organism, the research team found chondroitin from zebrafish tissues caused other fish to turn fin and run. They even took chondroitin from shark skin - the kind we take as supplements - and found that the zebrafish were terrified by it. The fish were also more afraid when the chondroitin was broken down by an enzyme first. The team hypothesized that when a fish is injured, enzymes released by the wounding break down chondroitin sulfate into smaller sugary chunks, and these bits and pieces, as well as the larger chondroitin molecules released by the wounded cells, are the smell that serves as a chemical alarm signal. The best part of this discovery is that it solves evolutionary issue that scientists have had with the existence of Schreckstoff. The burden of producing a fear signal while dying doesn't make sense unless that signal is something the fish already produced for other reasons which is only released in the case of injury - akin to some being afraid of the smell of blood. That way, the evolutionary impetus isn't on the fish producing Schreckstoff to produce an alarm, it's on other individuals to detect a sign of danger or death to save their own tails. Here's how it goes: once upon an evolutionary time, fish that were sensitive to Schreckstoff were the first to run in the face of danger, and thus were more likely to survive. Over time this would lead to an entire lineage of Schreckstoff-sensitive fish. Since chondroitin is a known component of fish skin for other reasons, but wouldn't be released into the water unless that skin is ruptured, it perfectly fits this evolutionary scenario.

Because young zebrafish are see-through, researchers were also able to specifically examine what parts of the zebrafish brain are turned on by chondroitin fragments. They found that a specialized part of the brain called the mediodorsal posterior region was responsible for the fearful reaction. What is particularly interesting about this chunk of brain matter is that it is packed with a group of neurons called crypt cells which have no other known function. Scientists have been trying to uncover what these strange neurons do for awhile, and this new discovery may hold the key. Co-author Suresh Jesuthasan thinks that these cells are a part of a special brain circuit which mediates the fish's innate fear response. Together, the new findings, published in Current Biology, are the pieces to the Schreckstoff puzzle that scientists have been trying to fit for decades. There are still questions to be answered, of course - how do certain species only respond to injuries by their own species and not those of others, for example? - but this new study has provided valuable insight into fear responses in fish, and perhaps opened up new doors in our understanding of how fear originates and is processed in animal brains. Article Link: Mathuru et al., Chondroitin Fragments Are Odorants that Trigger Fear Behavior in Fish, Current Biology (2012), doi:10.1016/j.cub.2012.01.06

Here's the researchers' video of the fear response: Zebrafish fear response to Schreckstoff

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