Study: Serotonin stabilizes social memories

Projections from the medial septum connect to the social memory center of the hippocampal brain. Credit: Xiaoting Wu / Nancy Pritzker Laboratory

Is there anyone who doesn’t want to remember the people they meet, even after a brief introduction?

A new study by scientists at Stanford University’s Utsai Neuroscience Institute has shown that this can be achieved by targeted brain stimulation. Serotonin system.

In a study published on October 6, 2021 NatureFor the first time, a team at Stanford University observed how the mouse brain forms memories of new acquaintances, demonstrating the ability of targeted drugs to selectively weaken or strengthen these social memories. ..

“We have identified neurons that appear to generate new engrams of the individual by telling them that they are interacting with new animals with different odors, different faces, different postures, etc.” , Dr. Robert Marenka, MD. Professor Nancy Friend Pritzker of Stanford Medical Psychiatry and Behavioral Sciences. “By adjusting its neural activity up and down, we were able to later change how well the animal remembered this new individual.”

“Like us, mice live Social group, And you need to be able to quickly remember whether another animal is a member of the family, a former invader, a potential spouse, etc. “New study. “This discovery is very exciting because it represents the very early stages of social memory, the ability to remember new individuals that can be built up by future experiences.”

This study adds to the growing number of studies by the Marenka Lab that show how serotonin and other neuromodulatory chemicals regulate. Social cognition It represents a promising step towards targeted therapies that are in the brain and may one day improve the disorder. Social function Disorders such as autism, depression, and post-traumatic stress disorder (PTSD).

How the brain creates documents

For years, neuroscientists have come closer to how the hippocampal neural circuits, the memory center of the brain, support the formation of multi-layered social memory. Wu, Malenka and colleagues wanted to know how these social “dociers” began when animals first encountered new individuals.

Wu’s researchers focused on a cluster of tear-shaped neurons near the center of the brain called the medial septum. This has been shown to be particularly active during social encounters between two unfamiliar mice.

To test whether the medial septal cells are involved in the ability of the animal to remember new individuals, the team genetically modified these cells, one activating the cells and the other switching. Became sensitive to pairs of custom drug compounds to cut. They then injected one of these drugs into the mice shortly before introducing them into unfamiliar mice.

Mice are usually very interested in touching whiskers and sniffing here and there when they first meet a new individual. However, after this initial investigation, animals return primarily to their work. The animals clearly remember this first encounter for at least 30 minutes, as meeting the same animals again hardly excites them: the same furry face I just met-what’s new to see here There is nothing.

However, when researchers used drugs to selectively inhibit medial septal neurons shortly before introducing new animals, they prevented the formation of these social memories. The first meeting was successful, but when the animals reunited only a few minutes later, the affected mice behaved as if they had never seen another animal.

Conversely, the use of another drug to selectively enhance medial septal activity during the animal’s first encounter caused super-strong social memory: mice usually within hours. Forget the first encounter, but these mice clearly recognized their new acquaintance 24 hours later.

After showing that these medial septal neurons are important for the formation of new social memory, researchers showed how these memories are preserved. They track the projections of medial septal neurons into areas of the hippocampus where social memory is believed to exist, and how activation of these projections during social encounters enhances synaptic connections in this area. I showed you what to do.

“Perhaps these enhanced connections represent the creation of new memories for this new individual, and the hippocampus can add more context to it if the animal encounters it again.”

A new role for serotonin in the formation of social memory

But the team wasn’t finished. They also wanted to know what causes the activity of medial septal cells during social encounters in the first place. Based on Marenka’s ever-growing research on the role of the neurotransmitter serotonin in social cognition, the team had a strong premonition of where to look.

Through a comprehensive series of experiments, researchers have demonstrated that serotonin-producing neurons in the brainstem release neuromodulatory chemicals throughout the brain during new social encounters. This release stimulates medial septal neurons via specific subtypes of serotonin-sensitive receptor molecules. And blocking either serotonin release in the medial septum or activation of this receptor molecule prevents the formation of new social memory.

Similarly, researchers enhance serotonin signaling during initial social encounters by stimulating serotonin-producing neurons in the brainstem or by injecting drugs that activate specific serotonin receptors directly inward. By doing so, the septum itself has been shown to be able to sustain social memory 10 times longer.

The discovery that the formation of new social memory depends on only one of the 16 serotonin receptor molecules adopted throughout the nervous system is promising for potential translation into human psychiatric disorders. Researchers say.

“We know that social memory problems can be problematic with disorders like depression and PTSD, where people misunderstand emotions and memories to different people in life. It’s possible, “said Wu. “The beauty of these discoveries is the use of drugs that target only this particular type of serotonin receptor in the medial septum, without affecting other serotonin signaling throughout the body. You can imagine improving. “

Serotonin is probably best known for its role in depression. Depression can sometimes be treated by increasing the levels of neuromodulators throughout the brain, but it is very difficult to identify the function of neurotransmitters. Neurotransmitters produced by clusters of neurons in the brainstem are released throughout the brain and nervous system and are associated with roles in the regulation of mood, hunger, aggression, sleep, nausea, and digestion.

“I think it’s becoming increasingly clear that giving neuromodulators like serotonin a” global “function is not justified. To understand their role in normal brain function and disease, it is necessary to understand the specific context of the brain region in which they operate. “Marenka said.

New research adds to the growing number of studies by the Marenka lab that seek to separate the specific role that the serotonin system plays in social cognitive dysfunction.

For example, 2018 Nature The paper showed How is the animal’s overall sociality regulated by the same subtype of serotonin receptors that act in a nearby brain region called the nucleus accumbens?Earlier this year, the lab had the same targeted drug that strengthened society memory Even in the current treatise Improved measures Sociable in half a dozen different mouse models of autism. And in a 2019 study, the group used the clear effect of the recreational drug MDMA (sometimes called molly or ecstasy) on serotonin signaling, without dangerous addiction, and the potential for social bonds. Showed how to isolate therapeutic enhancements.

“We are working to establish a basic understanding of neural functions that fail with mental disorders that affect sociality and cognition,” Marenka said. “I believe this is our only hope of establishing a cure for some of the most complex and debilitating symptoms of mental illness.”

Receptors associated with the neurotransmitter serotonin, which promotes memory formation

For more information:
Xiaoting Wu et al, 5-HT modulation of the medial septal circuit regulates the stability of social memory, Nature (2021). DOI: 10.1038 / s41586-021-03956-8

Quote: Study: Serotonin was acquired on October 18, 2021 from https: // (October 18, 2021) ) Stabilize

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