New imaging technique allows researchers to see gene expression in the brains of living mice in real time

A team at the University of Minnesota led by the Twin Cities has developed a new technique that allows scientists and engineers to visualize mRNA molecules in the brains of living mice for the first time. The research reveals new insights into how memories are formed and stored in the brain and could provide scientists with new information about diseases such as Alzheimer’s disease.

The newspaper is published in the Proceedings of the National Academy of Sciences (PNAS)†

There is still much mystery surrounding the process of how memory is physically made and stored in the brain† It is well known that mRNA – a type of RNA involved in the production of proteins – is produced during the process of forming and storing memories, but the technology to study this process at the cellular level is limited. Previous studies have often involved dissecting mice to examine their brains.

A team of researchers led by a faculty member from the University of Minnesota Twin Cities has developed a new technique that gives scientists a look at RNA synthesis in the brain of a mouse while it is still alive.

“We still know very little about memories in the brain,” explains Hye Yoon Park, an associate professor in the Department of Electrical and Computer Engineering at the University of Minnesota and the study’s lead author. “It is known that mRNA synthesis is important for memory, but it was never possible to image this in a living brain. Our work makes an important contribution to this field. We now have this new technology that neurobiologists can use.” for various experiments and memory tests in the future.”

The University of Minnesota-led team involved genetic engineering, two-photon excitation microscopy, and optimized image processing software. By genetically modifying a mouse to produce mRNA labeled with green fluorescent proteins (proteins derived from a jellyfish), the researchers were able to see when and where the mouse’s brain produced Arc mRNA, the specific type of molecule they were looking for. goods.

Because the mouse is alive, the researchers were able to study it longer. Using this new process, the researchers performed two experiments on the mouse in which they could see in real time what the neurons — or nerve cells — were doing for a month while the mouse was forming and storing memories.

Historically, neuroscientists have theorized that certain groups of neurons in the brain fire when a memory is formed, and that those same cells fire again when that moment or event is remembered. However, in both experiments, the researchers found that different groups of neurons fired each day that they activated memory in the mouse.

Over the course of several days after the mouse created this memory, they were able to locate a small group of cells that overlapped, or consistently produced the Arc mRNA every day, in the retrosplenial cortex (RSC) area of ​​the brain, a group they believe is responsible for the long-term storage of that memory.

“Our research is about memory generation and retrieval,” Park said. “If we can understand how this happens, it will help us a lot in understanding Alzheimer’s disease and other memory-related diseases. Maybe people with Alzheimer’s still store the memories somewhere — they just can’t get them back. So in the very long term, this research may help us overcome these diseases.”

In addition to Park, the team included researchers from Seoul National University, Byung Hun Lee, Jae Youn Shim, Hyungseok Moon, and Dong Wook Kim; and Korea Institute of Science and Technology researchers Jiwon Kim, Jang Soo Yook and Jinhyun Kim.