You can learn to be fearless

Katharina Spoida (left) and Sandra Süß have examined how the lack of a specific receptor affects the ability to unlearn fear.
Photo Credit: RUB, Marquard

The lack of a specific serotonin receptor helps to unlearn fear faster.

The messenger serotonin plays an important role in the development, but also in the learning of fear and fear. A research team in general zoology and neurobiology around Dr. Katharina Spoida and Dr. Sandra Süß examined in the collaborative research center "Extinction Learning" at the Ruhr University Bochum. The researchers were able to show that mice that lack a certain serotonin receptor unlearn fear much faster than the wild type. The results of the study provide a possible explanation of how drugs for post-traumatic stress disorders (PTSDs) change our brain activity. Those affected often have the ability to unlearn fear, making therapies difficult. The study was carried out on 19. November 2022 published in the journal Translational Psychiatry.

Everyday sensations cause fear

After a traumatic experience, those affected sometimes suffer fear long later, which is caused by certain sensory impressions from our everyday environment and is then overpowering. Post-traumatic stress disorder, or PTSD for short, is what experts call it. In this disorder, it is not or only with difficulty that those affected can unlearn the connection once they have learned between a neutral environmental stimulus and fear, which affects the success of therapies.

Knowing that serotonin messenger plays an important role in the development of fear, the research team got to the bottom of its role in learning extinction, unlearning fear. For this purpose, they examined so-called knock-out mice, which lack a certain serotonin receptor, the 5-HT2C receptor, due to genetic changes. These mice learned in one day to combine a certain tone with a slight but unpleasant current stimulus. "As a result of this learning process, the following day they showed a fear reaction, a motionless persistence, which we call freeze," explains Katharina Spoida.

The advantage is the lack of the receptor

In the next step, the researchers repeatedly played the sound to the mice without the current stimulus. "It was striking that the knock-out mice learned much faster that the sound is no reason for fear than mice without the genetic change," said Katharina Spoida. “In the absence of the serotonin receptor, there seems to be an advantage for learning to absorb."

The researchers continued to investigate this phenomenon and found that the knock-out mice have changes in their neuronal activity in two different areas of the brain. This includes a specific sub-region of the dorsal Raphe core (DRN), which is generally the main production site of serotonin in our brain. In addition, the researchers discovered a different neuronal activity in the so-called bed core of the Stria terminalis (BNST), which belongs to the expanded amygdala. “In the knock-out mice, we initially found a fundamentally increased activity in certain serotonin-producing cells of the dorsal raphe. In a further step we were able to show that the lack of the receptor also changes the neuronal activity in two sub-core of the BNST, which ultimately supports the learning of extinction,” says first author Sandra Süß. The research results also describe a connection between the two brain regions, which means that the scientists suspect that an interaction is important for the improved extinction learning.

Possible effects of medication uncovered

The results of the study may show how drugs used in the treatment of PTSD affect the brain regions examined. "There are already drugs in clinical use that regulate the amount of serotonin available, so-called selective serotonin reuptake inhibitors, SSRIs for short," explains Katharina Spoida.

“The prolonged use of these drugs means that the examined receptor becomes less responsive to serotonin, similar to our knock-out model. We therefore suspect that the changes described could be essential for the positive effects of SSRIs,” adds Sandra Süß. The scientists hope that their results will help to develop more targeted treatment strategies for PTSD patients in the future.

Funding

The work was funded by the German Research Foundation within the framework of Collaborative Research Centers 1280 (project number 316803389, project A07) and 874 (project number 122679504, project B10) as well as the projects DFG2471 / 23-1 and DFG2471 / 21-1.

Source/Credit: Ruhr University Bochum

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