11 July 2022

See how memory is formed

Biologists have learned to observe the expression of genes in the brains of living mice in real time

Tatiana Matveeva, "Scientific Russia"

A team from the University of Minnesota (USA) has developed a new technique that allows for the first time to visualize mRNA molecules in the brains of living mice. The study can help scientists learn more about the formation and storage of memory, as well as about diseases such as Alzheimer's disease, the press service of the university reports. The article was published in the journal PNAS (Lee et al., Real-time visualization of mRNA synthesis during memory formation in live mice).

In the process of forming and storing memories, mRNA is produced — a type of RNA involved in the creation of proteins. The technologies that allow us to study this process are still limited. Previously, mRNA synthesis could be observed in the mouse brain only after the death of a rodent. The new technique allows scientists to examine it in the brain of a mouse while it is still alive.

The technology includes genetic engineering, two-photon excitation microscopy and optimized image processing software. By genetically modifying the mouse so that it produces mRNA labeled with green fluorescent proteins (proteins derived from jellyfish), the researchers were able to see when and where the mouse brain generated Arc mRNA –the specific type of molecule they were looking for.

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Because the mouse was alive, the researchers could observe its brain longer than the brain of a dead mouse. Using this new process, the researchers conducted two experiments on rodents – and for a month they could observe in real time what the neurons were doing while the mouse was forming and storing memories.

It is assumed that certain groups of neurons in the brain are excited when a memory is formed, and that the same cells are activated again when the same moment or event is recalled. However, in both experiments, the researchers found that different groups of neurons were triggered every day when scientists evoked a memory in mice. 

Within a few days after the mice formed a memory, the scientists were able to detect a small group of cells that overlapped or continuously generated Arc mRNA every day in the area of the retrosplenial cortex (RSC) of the brain. Researchers believe that this zone is responsible for the long-term storage of this memory.

"Our research concerns the generation and retrieval of memories," the authors of the study note. – If we can understand how this happens, it will help us in understanding Alzheimer's disease and other memory-related diseases. Perhaps people with Alzheimer's disease still have memories somewhere - they just can't recover them. So in the very long term, this research may allow us to defeat these diseases."

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