Mouse models are central to drug development, including treatments for neurological disorders, such as Parkinson's disease. Such diseases often affect movement, and treatments may need to relieve symptoms such as tremors. To be able to model these diseases effectively in animal studies, we need to be able to track even the smallest of movements with accuracy and precision. Now, researchers at the Okinawa Institute of Science and Technology (OIST) have turned to Hollywood for inspiration.
In a new eNeuro publication, researchers from OIST's Neuronal Rhythms in Movement Unit introduce a mouse motion capture method which provides very high-resolution measurement of mouse movement. Their marker-based approach avoids the need for extensive data processing with AI or machine learning, and can capture high-quality data on complex movement, such as running or climbing.
"Marker-based motion capture is everywhere in the entertainment industry, for video gaming and major movies alike. With the accuracy in 3D tracking that it can provide, the technology could prove transformational to neuroscience." said Dr. Bogna Ignatowska-Jankowska, first author on this study. "However, although the field has long been interested in such methods, all other attempts have failed to get any quality data. This is because whilst larger animals are easier to motion capture, mice pose many challenges. Their size, their tendency to eat anything near them, plus the behavioral changes which present if something is stuck to them, have all hindered any attempts at mouse motion capture. Our new method avoids these pitfalls."
Experiments without walls
The researchers set up a series of cameras around three different open spaces - a flat surface, a treadmill, and a climbing wheel - to form the recording areas. These cameras detected reflections from markers: stainless steel, reflective-coated balls placed at carefully chosen points across the animal's body, to ensure full-body movement coverage. They needed to avoid having any walls within the experimental setup, so that the cameras could detect the reflections without interruption. Therefore, it was pivotal to acclimatize the mice to the markers and to ensure the animals were happy and didn't try to wander away from the cameras.
"We put a large emphasis on animal handling, to ensure this set up worked. Instead of using any sort of reward or punishment system, we just let the mice roam openly. This was also good for capturing natural movement and behavior, as well as keeping the mice stress-free," added Professor Yoe Uusisaari, head of the unit.
With 3D motion capture, the researchers were able to record both small tremors and large movements. Whilst the mice ran, climbed and explored, they were able to measure limb speed and step height, to build a detailed picture of natural mouse movement. The sensitivity of the method to small changes meant that the researchers were able to notice changes in movement that were barely detectable to the eye.
The researchers now look forward to harnessing the output of marker-based motion capture to gain better understanding of mouse behavior. Prof. Uusisaari said, "The data we produce has far less noise or error compared to any other methods. Using mathematical and computational models with such quality data, we can explore the neuroscientific and physiological foundations of how and why mice move in certain ways."
Brain mechanisms in motion
Different brain mechanisms are involved in different behaviors, whether automatic, like running on a treadmill, or exploratory, like moving freely about a space. By capturing detailed 3D data on mice doing different tasks, the researchers also hope to build better models of how certain brain regions might be affected by different drugs or diseases.
"Our lab is developing lots of different neuroscience methods, from motion capture to brain imaging. By combining these techniques, we'll be able to collect and analyze a variety of data. This has the potential to vastly improve our understanding of mice, and therefore also improve baseline models for animal studies in drug development," emphasized Dr. Ignatowska-Jankowska.
