Kizeev Gabrielle, Witteveen Isabelle, Balmer Timothy
School of Life Sciences, Arizona State University, Tempe, AZ, 85287, USA.
Cerebellum. 2024 Dec 19;24(1):16. doi: 10.1007/s12311-024-01767-x.
The vestibular processing regions of the cerebellum integrate vestibular information with other sensory modalities and motor signals to regulate balance, gaze stability, and spatial orientation. A class of excitatory glutamatergic interneurons known as unipolar brush cells (UBCs) are highly concentrated within the granule cell layer of these regions. UBCs receive vestibular signals directly from primary vestibular afferents and indirectly from mossy fibers. Each UBC excites numerous granule cells and could contribute to computations necessary for balance-related motor function. Prior research has implicated UBCs in motor function, but their influence on balance performance remains unclear, especially in aged mice that have age-related impairment. Here we tested whether UBCs contribute to motor coordination and balance by disrupting their activity with chemogenetics in aged and young mice. Age-related balance deficits were apparent in mice > 6 months old. Disrupting the activity of a subpopulation of UBCs caused aged mice to fall off a balance beam more frequently and altered swimming behaviors that are sensitive to vestibular dysfunction. These effects were not seen in young (7-week-old) mice. Thus, disrupting the activity of UBCs impairs mice with age-related balance issues and suggest that UBCs are essential for balance and vestibular function in aged mice.
小脑的前庭处理区域将前庭信息与其他感觉模态及运动信号整合起来，以调节平衡、注视稳定性和空间定向。一类被称为单极刷状细胞（UBCs）的兴奋性谷氨酸能中间神经元高度集中在这些区域的颗粒细胞层内。UBCs直接从前庭初级传入纤维接收前庭信号，并间接从苔藓纤维接收信号。每个UBCs会兴奋大量颗粒细胞，并可能有助于与平衡相关的运动功能所需的计算。先前的研究表明UBCs与运动功能有关，但其对平衡表现的影响仍不清楚，尤其是在患有与年龄相关损伤的老年小鼠中。在这里，我们通过在老年和年轻小鼠中利用化学遗传学破坏UBCs的活性，来测试它们是否有助于运动协调和平衡。6个月以上的小鼠出现了与年龄相关的平衡缺陷。破坏一部分UBCs的活性会导致老年小鼠更频繁地从平衡木上掉落，并改变对前庭功能障碍敏感的游泳行为。在年轻（7周龄）小鼠中未观察到这些影响。因此，破坏UBCs的活性会损害患有与年龄相关平衡问题的小鼠，并表明UBCs对老年小鼠的平衡和前庭功能至关重要。
