Task-related activation of the non-human primate cerebellum during normal aging
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Abstract
The exact relationship between the cerebellum and cognitive processing is unknown. In recent years, evidence has shown there is a significant impact in the posterior cerebellum due to the progression of neurodegenerative conditions such as cerebellar cognitive affective syndrome and Alzheimer’s Disease, indicating it could possibly serve a modulatory role in cognitive functioning. This has led to increasing interest in how the cerebellum and cognition are related and the impact it has on cognitive performance. As cognition is often affected in aging individuals and the cerebellum has been shown to change greatly with increasing age, there is also a growing interest in determining whether age has an impact on cognitive performance due to changes in the cerebellum. Using the Rhesus monkey as a model system, this study will examine whether there is a pattern of activation in the posterior cerebellum while performing a cognitive task. There are two objectives for this study:(a) determine the specific cells and regions that are active during such a task and (b) determine whether there are any age-related changes in the posterior cerebellum and whether cerebellar activation patterns relate to cognitive impairment indices in aged animals. We hypothesize that performance of a cognitive task will result in activation of the posterior lobe in the cerebellar cortex and that this same region will show a reduced activation in aged animals who have high cognitive impairment indices (CIIs). We will do this by using immunohistochemistry (IHC) with c-Fos antibody. c-Fos is an immediate early gene upregulated in neurons when they are active. We will quantify neuronal activation in the posterior cerebellar lobes. Additionally, these data will be correlated with age and cognitive impairment index in these animals. We found that performance on a cognitive task was associated with regionally specific activation in the cerebellar cortex and in the deep cerebellar nuclei. Clusters of Purkinje cells and granule cells were activated during the task. Activation was not active throughout the entirety of lobule VIIA. In most of the monkeys tested in this study, there was more activation of Purkinje cells on the side of the lobule closest to Crus I, whereas on the other side there was only some activation. Additionally, granule cell activation appeared in clusters near activated Purkinje cells, however, these cells were not active in all regions where Purkinje cells were active. In monkeys who performed a behavioral task, it was apparent that there was greater activation in one hemisphere than the other, whereas those who did not perform a task showed little difference between the two hemispheres. This study provides further evidence that there is activation of the posterior lobe in the cerebellum during the execution of a cognitive task. As such, in future studies, the role the posterior cerebellum and, specifically, the activation of Purkinje cells play in cognitive function could be a key factor in understanding how they may affect the prognosis of neurodegenerative conditions.
Description
2024