Health | An experiment conducted on rats showed that the formation of extinction memory, which is responsible for reducing fear, occurs through different serotonin receptors in the prefrontal cortex of animals who are either alone or accompanied
*By: Alexandre Briozo Gomes Filho
*First published: April 25, 2024
*Photo: Marcelo Pires/JU
It was drizzling when I noticed two shadows approaching me from behind at the corner of Ipiranga Avenue and Ramiro Barcelos Street, near the UFRGS Institute of Health Sciences. The sharp edge of a knife pressed against my stomach is still a vivid sensation in my memory. The menacing look of the robbers made it clear that they were not joking. I would either hand over my phone or get stabbed. I did not fight. “Just walk away quietly and don’t look back,” one of them said after grabbing the phone from my pocket. It happened the same way on two occasions last year, five months apart. Both times, I got robbed of a phone and of the sense of security I once had walking through the city. I stored fear memories.
In the following days, isolation seemed like the only possible solution. Walking alone on the street was unthinkable. When it was unavoidably necessary, I would freeze behind my door before I could finally do it. In the company of a friend, the situation used to be completely different: the sense of security would return. I began to counteract the fear memory with an extinction memory, formed to lessen the fear.
The fear experience I went through is an example of what was explored in a study conducted by the Graduate Program in Translational Neuroscience at the Federal University of Rio de Janeiro (UFRJ), in collaboration with the Neuroprotection and Metabolic Diseases Laboratory at the Institute of Basic Health Sciences (ICBS) at UFRGS. Derived from the doctoral thesis of neuroscientist Clarissa Penha Farias, the article, published in Behavioural Brain Research, investigates the differences in the formation of extinction memory in Wistar rats that were either accompanied by another animal (social support) or alone. The research was supervised by Angela Wyse, a professor in the Department of Biochemistry at UFRGS.
The study, which took a translational approach, focused on three serotonin receptors (5-HT2A, 5-HT5A, and 5-HT6) in the prefrontal cortex. It was observed that in the group of rats accompanied by another animal, the formation of extinction memory depended on different serotonin receptors than those activated in the group of rats that underwent the experiment alone.
Understanding Freezing
“We decided to work with the prefrontal cortex because we had previously observed that this [fear] memory depended on this structure,” says Farias. The researcher began studying the impact of social support on the extinction of fear memory during her master’s training program. At the time, the study focused on whether animals that had been accompanied reacted differently than those which had been left alone when exposed to electric stimuli, which is a behavioral task that induces fear. In the experiment, the rats that had undergone this task alone expressed what is called freezing, an absence of movement where the animal becomes “motionless still,” only breathing.
“First, the animal needs to evoke the fear memory, which is represented by freezing. Over time, as it realizes it no longer receives the electric stimulus, it begins to reduce this expression of fear,” explains the neuroscientist. When accompanied by another rat, the freezing expressed by the animal was significantly reduced.
“Through our experiences, we see that fears are important. But they can also be incapacitating and limiting”
Clarissa Penha Farias
As Farias advanced to her doctoral studies, the research became more complex. The focus shifted to understanding the neurological mechanisms responsible for the reduction in freezing when there is social support. Initially supervised by memory specialist Ivan Izquierdo from PUCRS, Farias was later supervised by Professor Angela Wyse following Izquierdo’s death in 2021. A researcher in biochemistry and neuroscience with a focus on memory and behavior, Wyse took over the supervision of Izquierdo’s doctoral students and continued the projects while adding necessary contributions as the research progressed. Furthermore, Wyse became affiliated with the Graduate Program in Translational Neuroscience at UFRJ. “It is very important that we collaborate with one another, and we have a network experience. It always adds to our knowledge building,” says the UFRGS professor.
Under Wyse’s supervision, Farias conducted a behavioral experiment over three days with 60-day-old male Wistar rats, both alone and accompanied. In the fear conditioning process, each animal received an electric stimulus and then underwent extinction training, where it was placed in the apparatus without receiving the stimulus. It was during this stage that the animal with a companion showed a reduction in freezing.
Following the extinction training, antagonistic drugs for the selected receptors were infused. Twenty-four hours later, the animals were tested, and the researchers found that the extinction memory in the rats with social support was dependent on different receptors than those activated in the rats that underwent the training alone.
“Having someone that you trust by your side makes you more self-confident. You feel safer, and that reduces your fears”
Angela Wyse
Dealing with Fear and Looking to the Future
Despite the conclusions, finding ways to make extinction memory more durable is still left to be done, as it does not last long, what allows the fear to return. “Let’s say I fear cockroaches. I go through cognitive-behavioral therapy and reinterpret my fear perception to one that believes cockroaches are not dangerous to me. I can maintain that belief for a period of time, but that does not stop me from seeing a tiny bit of a cockroach antennae and urging to run away,” Farias explains.
As Wyse points out, fear is an important survival tool, as long as it is not excessive. “When fear becomes exaggerated, it can lead to phobias, depression, and anxiety,” she observes. Once the mechanism for the duration of extinction memory is understood, it will be possible to extend this memory in situations of excessive fear, helping people manage the emotion better.
In Faria’s office in the Department of Biochemistry at UFRGS, the mentor and her student discuss what lies ahead. Continuing the study of social support in overcoming fear memory is Faria’s goal for her future postdoctoral training.
*Faria’s doctoral dissertation will soon be available on Lume – the UFRGS Digital Repository.
Translated into English by Jennifer Folharini Mesquita, undergraduate student enrolled in the course “Supervised Translation Training II (English)” of the Undergraduate Program in Language and Literature, under the supervision and translation revision of Professor Elizamari R. Becker (P.h.D.) – IL/UFRGS.