A new imaging technique allows researchers to see gene expression in the brains of living mice in real time
A team led by the University of Minnesota’s Twin Cities has developed a new technique that allows scientists and engineers, for the first time, to visualize mRNA molecules in the brains of living mice. This research reveals new insights into how memories are formed and stored in the brain and could provide scientists with new information about diseases like Alzheimer’s.
The paper is published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), a peer-reviewed, multidisciplinary, high-impact scientific journal.
There are still many mysteries surrounding the process of how memories are physically created and stored in the brain. It is well known that mRNA—a type of RNA involved in making proteins—is produced during the processes of memory formation and storage, but the technology for studying this process at the cellular level is still limited. Previous research has often involved dissecting mice to examine their brains.
A research team led by University of Minnesota Twin Cities faculty members has developed a new technique that gives scientists a window into RNA synthesis in the brains of living mice.
“We still know very little about memory in the brain,” explains Hye Yoon Park, a professor in the University of Minnesota’s Department of Electrical and Computer Engineering and lead author of the study. “It is well known that mRNA synthesis is important for memory, but it was never possible to imagine this in the living brain. Our work is an important contribution to this field. We now have new technology that neurobiologists can use for different experiments and future memory tests.”
The University of Minnesota-led team process involved genetic engineering, a two-photon excitation microscope, and optimized image processing software. By genetically modifying the mice to produce mRNA labeled with a green fluorescent protein (a protein derived from jellyfish), the researchers were able to see when and where the mice’s brains produced Arc mRNA, the specific type of molecule they were looking for.
Because the mice were alive, the researchers were able to study them for a longer period of time. Using this new process, the researchers conducted two experiments on mice in which they were able to see in real time for a month what neurons — or nerve cells — were doing as the mice formed and stored 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 were triggered each day they triggered memory in mice.
For several days after the mice created this memory, they were able to find a small cluster of cells that overlapped, or consistently produced Arc mRNA daily, in the retrosplenial cortex (RSC) region of the brain, a group they believe is responsible for the long-term storage of memory. that.
“Our research is about memory creation and retrieval,” Park said. “If we can understand how this happens, it will help us greatly in understanding Alzheimer’s disease and other memory-related diseases. Maybe people with Alzheimer’s disease still have memories somewhere—they can’t recall them. So in the long term, maybe this research can help us deal with those diseases.”
This research was funded by the Samsung Science and Technology Foundation and the Welcome Trust.
In addition to Park, the team included Seoul National University researchers Byung Hun Lee, Jae Youn Shim, Hyungseok Moon, and Dong Wook Kim; and Korean Institute of Science and Technology researchers Jiwon Kim, Jang Soo Yook, and Jinhyun Kim.
Watch a 3D video that visualizes the hippocampus region of a live mouse brain.
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