New Method Reveals Brain activity with single-Cell Resolution

An international team led by the University of Michigan has introduced new methods that reveal which regions of the brain were active throughout the day with single-cell resolution.

Using mouse models, the researchers developed an experimental protocol and a computational analysis to follow which neurons and networks within the brain were active at different times. Published in the journal PLOS Biology, the study provides new insights into brain signaling during sleep and wakefulness, which hints at the bigger questions and goals that motivated the work.

We undertook this tough study to understand fatigue.We’re seeing profound changes in the brain over the course of the day as we stay awake and thay seem to be corrected as we go to sleep.

Daniel Forger, U-M professor of mathematics, senior author

What the team found and how they found it could help lead to new ways to objectively assess fatigue in humans. These could in turn be used to help ensure people with high-stakes responsibilities, such as pilots and surgeons, are adequately rested before starting a flight or an operation.

“We’re actually terrible judges of our own fatigue. It’s based on our subjective tiredness,” Forger said. “Our hope is that we can develop ‘signatures’ that will tell us if people are particularly fatigued, and whether they can do their jobs safely.”

The study was supported by federal funding from the U.S. National Science Foundation and the U.S. Army Research office. It also received funding from the Human Frontier Science Program, or HFSP, that enables pioneering work in the life sciences through international collaboration, which was key to this study.

A more global view

While researchers at U-M created the mathematical and computational workflows to analyze and interpret data, collaborators in Japan and Switzerland were developing a powerful new experimental approach.

They leveraged a cutting-edge form of imaging called light sheet microscopy that enabled them to generate 3D images of mouse brains.They also introduced a genetic tagging method that resulted in active neurons glowing under the microscope, allowing the researchers to see which cells were active across the brain and when.

“We certainly know from studies over the last 20 or 30 years,how to decipher how one aspect-a gene or a type of neuron,as a notable example-can contribute to behavior