Researchers developed new experimental and computational methods to map brain activity with single-cell detail across the day in mouse models. The team combined a laboratory protocol that genetically tags active neurons with mathematical and computational workflows to track neurons and networks over time. Collaborators in three countries provided different parts of the work: University of Michigan researchers built the computational pipelines, while groups in Japan and Switzerland provided the experimental tools.
The Japanese team led by Hiroki Ueda at RIKEN used light-sheet microscopy to produce three-dimensional images of mouse brains. The genetic tagging method made active neurons glow under the microscope, allowing researchers to see both when and where cells were active. The main finding was a consistent reorganisation of activity across the daily cycle: as mice woke, activity tended to begin in inner, subcortical layers and, over the course of day or night, hubs of activity moved toward the cortical surface.
The study was partly motivated by a desire to understand fatigue. Daniel Forger, senior author and professor at the University of Michigan, said the team hopes to develop signatures that indicate when people are particularly fatigued, which could help assess readiness for high-stakes jobs such as flying or surgery. Konstantinos Kompotis of the University of Zurich emphasised that behaviour arises from many interacting elements across the brain. Although the imaging methods cannot be used directly in humans, coauthor Guanhua Sun said the mathematics are simple and the approach could be adapted to coarser human data from EEG, PET or MRI and to other animal models for diseases such as Alzheimer’s and Parkinson’s. Kompotis is working with industry partners to test how therapeutics affect brain activity. The team dedicated the study to Steven Brown, a senior coauthor who died in a plane crash, and the work received funding from the US National Science Foundation, the US Army Research Office and the Human Frontier Science Program.
Difficult words
- computational — relating to the use of computers
- pipeline — sequence of processing steps or taskspipelines
- genetic tagging — marking cells using genes to track
- light-sheet microscopy — microscope method using thin light sheets
- reorganisation — change in the arrangement or structure
- subcortical — located below the brain cortex
- cortical — related to the brain's outer layer
- fatigue — strong tiredness or reduced energy
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could signatures of fatigue based on brain activity affect safety in high-stakes jobs?
- What are the challenges of adapting methods developed in mice to coarser human data like EEG or MRI?
- Do you think industry partnerships for testing therapeutics can change how this research is used? Why or why not?
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