As part of his Erwin Schrödinger scholarship, Florian Reichmann went to England to look for genes for aggressive behavior. To this end, he examined the behavior of zebrafish and found differences in the brain in particularly peaceful and particularly aggressive breeding lines.
How long does it take for a zebrafish to let go of its own reflection in the mirror? How quickly does the fish start to attack the supposed opponent, how long does it snap and follow it with typical swimming movements in a time interval? The longer the period of time, the greater the “fighter nature”. For Florian Reichmann, pharmacologist at the Medical University of Graz, the time measured in the “mirror test” was the measure of all things for his investigations into the genetic influences on aggressive behavior in zebrafish. As a Schrödinger scholarship holder of the Austrian Science Fund FWF, the Styrian spent two years doing research in Will Norton’s group at the University of Leicester in England. The advantage of the mirror test is that young and adult zebrafish, both males and females, can be tested and the animals are not injured in the process.
Aggression and histamine regulation
Zebrafish, the real name for the fish from the carp family, are not only popular ornamental fish, but also a love of genetics. Around 70 percent of the zebrafish genes are found in a similar form in humans. Schooling fish with high fertility and rapid growth also prove to be a suitable model for behavioral research. Supported by the FWF, Florian Reichmann pursued two different research approaches in his project. On the one hand, in Will Norton’s laboratory, the CRISPR / Cas9 (“gene scissors”) tool was used to create a fish line that does not develop an H3 receptor in the brain. This histamine receptor had emerged as a candidate for the regulation of aggressive behavior in previous studies.
In order to describe possible changes in behavior of the H3 mutants or to compare them with the wild type (with H3 receptor), Reichmann then filmed the fish with high-resolution cameras and observed the following: “As early as four days, the individuals showed little mobility in free swimming and more afraid. The fish without an H3 receptor also reacted in a frightened and fearful way to a threatening video stimulus, whereby the adult H3 mutants are even less aggressive compared to the young can be measured with the microscope. For this, in turn, a cooperation with the University of Exeter was crucial – and the transport of the juveniles across England. In the adult fish with and without the H3 receptor, differences in activity in numerous areas of the brain could be detected. Immediately after encountering the mirror test, the brain tissue of both lines was examined to identify those areas that are activated by aggression.
Genetic differences in peaceable and fighter natures
In the second research approach, the project manager bred very “peaceful” and very “combative” lines of fish over several generations. Among other things, it has been proven that aggressive behavior can also be inherited in fish: “According to our mirror tests, we have bred the most aggressive and the most peaceful fish over four generations. Then we looked for differences in genetic activation in the genome, i.e. the entirety of the genetic material, using RNA sequencing. ”The result: The two lines differed greatly – in around 500 genes. The analysis suggests that genes related to the immune system are relevant and more pronounced in aggressive fish. One gene for arsenic metabolism, which has not yet been characterized, was the most significant. In humans, this gene was also found in connection with the clinical picture of schizophrenia.
Reichmann and his research colleagues have thus succeeded in taking an important step forward in behavioral research. Their results show that aggression in zebrafish has a strong genetic basis and that the H3 receptor plays an important role in this. Ultimately, this can help to replace the sedatives that have so far been widely used with targeted drugs against highly aggressive behavior. But there is still a long way to go before then. Florian Reichmann will use the time and wants to establish a zebrafish group back at the Medical University of Graz.
Profile: Florian Reichmann
Florian Reichmann studied human medicine and completed a doctorate in neuroscience at the Medical University of Graz. He completed his postdoc at the Institute for Experimental and Clinical Pharmacology and carried out research as an Erwin Schrödinger fellow from 2017 to 2019 at the University of Leicester (UK). Since August 2020 he has been researching the genetic and neurobiological basis of emotional-affective, social and cognitive behavior in the context of neuropsychiatric diseases with various model organisms at the Otto Loewi Research Center at the Medical University of Graz. The project “Genetic and environmental factors of aggression in zebrafish” was funded with 170,000 euros by the FWF Science Fund.
Proof of text: FWF
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