Balance in Older Mice Relies on Specific Brain Cells
By Timothy Balmer, Ph.D.
The cerebellum is a part of the brain that is important for producing smooth movements in all vertebrate animals, including humans. The vestibular cerebellum is a region within the cerebellum that processes head movement-related signals and integrates them with signals from other sensory systems.
This part of the cerebellum is essential for balance, posture, eye movements, and to an animal’s perception of their body’s position in space. When the vestibular cerebellum is damaged by trauma or disease, symptoms result, including instability, nystagmus (a disorder of eye movements), ataxia (a disorder of muscle movements), or vertigo (a disorder of the perception of head movements). All of these impairments can result in falls, which is a leading cause of injury in the elderly.
The vestibular cerebellum has a particularly high density of unipolar brush cells, which are neurons that are positioned in the neural circuitry in such a way that suggests that they may be important for the processing and amplification of vestibular signals.
These cells receive vestibular signals from the semicircular canals and from the brainstem, process the information, and expand its representation to downstream neurons. However, despite their number in the vestibular cerebellum, the role of unipolar brush cells in behaviors relevant to balance and vestibular function is unclear.
Using CNO (clozapine-N-oxide, a chemogenetic activator), the researchers disrupted unipolar brush cell (UPC) activity in mice. Older mice struggled more with balance and movement, showing more falls and slower walking, while younger mice and controls were unaffected. This highlights the importance of UBCs in maintaining balance as mice age. Credit: Kizeev, Witteveen, Balmer/The Cerebellum
The aim of our study, whose results were published in The Cerebellum in December 2024, was to test the contribution of unipolar brush cells to balance behaviors in mice. We used three behavioral tests to measure balance: a rotating horizontal rod, a narrow balance beam, and a swimming test.
The mice in this study were engineered to allow us to manipulate the electrical activity of unipolar brush cells at a specific time during the study. We first measured the mice’s balance and swimming behavior, then altered the activity of the unipolar brush cells and tested them again to determine the importance of these cells in the performance of these behaviors.
Interestingly, we found that the impairment was only present in older mice that had evidence of age-related balance difficulty, but not in younger mice. This study suggests that this class of neurons may compensate for age-related loss of vestibular function to maintain balance performance in older animals.
It will be important to test this idea with other complimentary approaches, to detail the role of different types of unipolar brush cells further, and to determine what caused the impairment that we detected here. Were the mice unable to move appropriately, or did they misunderstand their orientation in space?
Moving forward, we would like to test whether balance performance of older animals can be improved by manipulating the activity of these cells. On a more fundamental level, understanding how the vestibular cerebellum functions is essential to develop strategies to overcome age-related balance impairments and other disorders of balance and vestibular function that can lead to injury.
Timothy Balmer, Ph.D., is an assistant professor in the School of Life Sciences at Arizona State University. He is a 2025 Emerging Research Grants (ERG) scientist generously funded by the Salice Family Foundation. This paper is funded in part by his 2022–2023 ERG grant generously underwritten by an anonymous donor. Balmer is also a 2017 ERG scientist generously funded by the Les Paul Foundation.