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Categories: Brain Chondroitin Fragments Chondroitin sulfate Developmental Neuroscience Fish Fish Fear Factor GAGs Glycosoaminoglycan Marine Science Schreckstoff

Singapore Scientists Discover Fish Fear Factor

Research breakthrough provides insights to a 70-year-old puzzle on the nature of the fish alarm signal

Scientists from the Agency of Science, Technology and Research’s Neuroscience Research Partnership and the Duke-National University of Singapore Graduate Medical School have figured out the nature of “Schreckstoff”[1] (German for alarm substance or scary stuff) that causes the rest of a school of fish to take off in fear when one member gets injured.

The team of scientists, led by Dr Suresh Jesuthasan, Principal Investigator from the A*STAR Neuroscience Research Partnership, have shown that one component of the alarm substance is a class of sugars – specifically a type of glycosoaminoglycan (GAG) called chondroitin sulfate. When a fish is injured, it causes the breakdown of this sugar, which is found in abundance in the skin, and it is the fragments that cause the fear response.

The researchers used brain imaging to see how alarm signals are processed in the brain. It was discovered that one region in the olfactory bulb – the part of the brain which first processes smell – is activated by the GAGs. This region is special in several ways: Signals reach there by means of special receptor neurons - the “crypt cells”, implying that there are neurons dedicated to sensing the alarm pheromone; also, this region connects to unique higher centers of the brain, suggesting that there may be a special brain circuit mediating aspects of the innate fear response.

The findings also help to explain how this “danger” signal might have evolved though the sender, the injured fish, does not stand to benefit. The sugar fragments are naturally released upon injury and fish that are able to smell the fragments and flee would have a higher chance for survival and breeding.

However, the researchers have noted that the alarm response itself begs further exploration. Different concentrations of the alarm substance cause different fear responses – low concentrations trigger mild fear characterized by darting while high concentrations cause freezing. Dr Suresh said, “How the brain switches from one fear state to another is an interesting question, with relevance to anxiety disorders. By using the alarm response, we have a reliable way to investigate the neural basis of differential fear responses.”

The researchers highlighted that there is still much work to be done, for example, discovering the receptor for these glycan fragments. The potential application of this discovery can extend to other fields of biology such as developmental neuroscience, where chondroitin fragments function as signaling molecules.

Prof Dale Purves, Program Director of the Neurosciences and Behavioral Disorders Program at Duke-NUS Graduate Medical School and Executive Director of theA*STAR-Duke-NUS GMS NRP, commented, “Studying the fear behaviour in a tiny fish may seem somewhat simplistic but such animal models can offer important insights into more complex human disorders. This important work by Dr.Jesuthasan and his colleagues is an excellent example of this.”


The research findings can be found in the 20 March 2012 issue of the Current Biology under the title, “Chondroitin Fragments Are Odorants that Trigger Fear Behavior in Fish” by Ajay S. Mathuru 1, Caroline Kibat 1 ,Wei Fun Cheong 2, Guanghou Shui 2,4 , Markus R. Wenk 2,5, Rainer W. Friedrich 6,7and Suresh Jesuthasan 1,3,8,*

 1 Biomedical Sciences Institutes, Neuroscience Research Partnership
2 Department of Biochemistry, National University of Singapore
3 Department of Physiology, National University of Singapore
4 Neurobiology Program, Life Science Institute, National University of Singapore
5 Department of Biological Sciences, National University of Singapore
6Friedrich Miescher Institute for Biomedical Research
7University of Basel
8Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School

Contact: Umadevi Kanagalingam (Ms), Tel: +65 6826 6321, Email:

Source: Agency for Science, Technology and Research (A*STAR)

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