Mice tails whip up new insights into balance and neurodegenerative disease research

The answer to this is not as simple as you might think. New research from the Okinawa Institute of Science and Technology (OIST) has shown that there's more to the humble mouse tail than previously assumed. Using a novel experimental setup involving a tilting platform, high-speed videography and mathematical modelling, scientists have demonstrated how mice swing their tails like a whip to maintain balance -- and these findings can help us better understand balance issues in humans, paving the way for spotting and treating neurodegenerative diseases like multiple sclerosis and Parkinson's disease at earlier stages.

"Mice are ubiquitous in neuroscience because of their genetic, biological and behavioral similarity to us, and yet the role of their characteristic tail has remained elusive," explains Dr. Salvatore Lacava from the Neuronal Rhythms in Movement Unit at OIST and first author on the study now published in the Journal of Experimental Biology. "By getting a deeper understanding of how healthy mice balance and by improving the ways in which we assess their performance, we can better explore the neurological mechanisms behind, as well as potential treatments for, conditions that affect motor control and stability."

Balancing with a flick of the tail

It has long been assumed that mice use their tail as a passive counterweight, like how you might lower your body on a bicycle when riding over difficult terrain or in sharp turns. "We spent a lot of time observing healthy mice," recounts Dr. Lacava. "But instead of a passive use as a counterweight, we were surprised to find a consistently active use of their tail in maintaining balance." To regain their balance when the surface underneath them tilts, the researchers found that mice rotate their tail extremely quickly in the opposite direction of the tilt. Even though their tail is light, the sheer speed of the tail swing produces a significant amount of angular momentum, pulling their body away from the fall. "It would be like if you could swing a whip fast enough to pull yourself in the direction of the crack to avoid falling backwards."

In addition to sudden shifts in balance, they also found that mice use their tail to remain balanced when going across narrow platforms. Here, the tail is continuously flicked in the opposite direction of the movements of the body, mitigating the changes in balance as the mouse moves. During the most challenging trials, the tail is also kept at a lower angle, supplementing the active use with the passive use as a counterweight.

Previously, the role of mice tails in maintaining balance was poorly understood and often overlooked in experiments. "While mice are crucial in neuroscience because of their likeness to us, our study underscores the importance of counting factors that we humans may not have -- like a tail -- but which impacts the research into conditions that do affect us," points out Professor Marylka Yoe Uusisaari, leader of the unit and senior author on the paper. In demonstrating the active role of mice tails, this study paves the way for more accurate measurements of balance performance in healthy mice, setting a solid benchmark for research into various conditions that affect balance, such as neurodegenerative diseases.

A challenge to mice and research

In addition to elucidating the role of mice tails, the researchers also developed a new experimental setup for assessing mouse balance. The previous standard is a beam-walking test, where mice are tasked with crossing a 1cm wide ridge under various conditions. If the mouse fell off, they were counted as being off-balance. But for healthy mice, this test is a cakewalk. As Prof. Uusisaari explains, "most mice species are arboreal animals, living in trees. They have adapted to swiftly cross difficult surfaces like thin branches. Our new setup accounts for this by challenging the mice with narrower surfaces and sudden movements."

The new setup uses a range of platform widths, from 1cm down to 4mm, as well as random 10-to-30-degree rotations in either direction. And instead of evaluating balance as the ability of being able to stay on the ridge, the researchers redefined balance as a metric of how well the mouse's body is positioned over its feet. To capture these finer nuances of the movements, the researchers created a biomechanical model based on a neural network trained to track the position of different parts of the mouse as it traverses the platform. This model allowed the researchers to calculate the angular momentum of the tail relative to the tilt of the body, showing how it counteracts the tilt.

"We want to be able to spot and treat balancing issues in humans before they become so severe that the patient struggles to walk in a straight line," summarizes Dr. Lacava. "With this study, we have now set the same standard for the mice." By demonstrating the role of mice tails in movement, and by raising the experimental bar for healthy mice, researchers are now better equipped to assess subtle changes in balance performance, allowing for much greater precision in studying the early effects of neurodegenerative diseases.