Non-invasive technology maps brain activity in mice

The new method will be used to study the brain processes that drive behaviors, raising hope for treating neurologic disease in people

Image above: New technology allows scientists to map brain without obtrusive devices. These images from the same brain region of the same mouse, which were acquired 24 hours after the recording of object recognition and rotorod tasks.

A research team led by Cleveland Clinic and Oregon Health & Science University has developed a new method for mapping how parts of the brain “speak” to each other, which is critical to understanding behavior changes in patients with neurologic disease.

Their findings published Oct. 12 in the journal Nature Communications.

The study describes a new method of recording brain activity patterns in freely moving mice. This, in turn, will enable scientists to deepen their understanding of the brain so that they can eventually develop new ways of testing and treating people with neurologic diseases.

Diseases like Alzheimer’s disease change how patients communicate and act, affecting their relationships and well-being. Cleveland Clinic’s Hod Dana, Ph.D., is collaborating with Jacob Raber, Ph.D, professor of behavioral neuroscience in the OHSU School of Medicine, on mapping out the electrical paths that connect and coordinate the various parts of our brains needed to complete different tasks.

“We now have the capability to study the relationship between brain activation and cognitive performance at an unprecedented level,” Raber said. “We can now identify in preclinical models how brain activity patterns during cognitive tests are altered with age and in neurological conditions. We can also see how brain activity patterns relate to behavioral and cognitive performance.

“These are the first steps in developing strategies to reverse those changes and improve cognitive performance in those affected by neurologic conditions. The future of behavioral and cognitive neuroscience looks bright.”

The team used a calcium sensor system called CaMPARI (Calcium-modulated photoactivatable ratiometric integrator) to map brain activity while completing cognitive tasks. Dana and Raber plan to use CaMPARI in preclinical work to see how Alzheimer’s-related genes affect the way our neurons signal through our brains in learning and memory.

Decision making, forming a memory or completing a task all involve brainwaves, signaling pathways using cells called neurons. To study how brainwaves influence behavior and decision making, researchers observe as neurons turn “on” and “off” across the organ in different situations. Current technologies are unable to map the whole brain while still identifying the single cells. CaMPARI images can be captured during behavior and highlight neurons that are active as red and inactive neurons as green. After the test is completed, the red and green markers remain bright for several days, allowing researchers to capture a series of images to track the brain’s activity through mapping where the red appears within the brain.

“Effects on behavior and personality in Alzheimer’s disease and related disorders are caused by changes in brain function,” Dana said. “If we can understand exactly how the changes occur, we may figure out how to slow down the process or stop it. Recording brain activity patterns that underlie behavioral changes is the first step to bridging the gap.”

The use of CaMPARI for recording also does not require focusing a microscope on the head while performing a behavioral task, which Dana said can affect the results and the interpretation of the data.

“As scientists, we want to study the brain in its most natural state possible, without biasing it with our own tools. CaMPARI lets us map behavior-specific pathways in the brain without using obtrusive devices or limiting our field of view,” Dana said. “It’s flexible, and can be used to look at neuronal activity under various conditions. The results are reliable and reproducible, and it is easy to implement with commonly used scientific setup.”

Dana and Raber say they hope to take what they learn from their results to develop tests and interventions that can improve the quality of life for humans, providing patients with better treatment options.


Funding support was provided by the National Institutes of Health under award numbers R21AG065914 and U01NS123658. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. No live animal work may be conducted at OHSU without IACUC approval.

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