Date of Award

5-2021

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Huo Lu PhD

Second Advisor

Richard White PhD

Third Advisor

Francis Jenney, PhD

Comments

The role of the cerebellum in balance and coordination of movement is universally accepted by researchers, but the mechanisms underlying this role remain elusive. There is evidence to suggest that cerebellar Purkinje cells have a role as the computational center of the cerebellar cortex, however the link between Purkinje cell function and animal behavior is not fully understood. The primary aim of this study is to observe the behavioral and neuronal changes associated with electric stimulation of the cerebellar cortex in normal and ataxic mice. All mice used for this research were trained to walk on a self propelled wheel for a duration of up to one hour. Video recordings were taken during the behavior task. Video data was later analyzed using DeepLabCut, a markerless pose estimation program. The key finding of this study was that there was a significant difference between control and ataxic mice in both local field potential and corresponding behavior. Furthermore, the frequency of local field potential activity correlated with the frequency of behavior for both control and ataxic mice. Electric stimulation of the cerebellar cortex did not cause significant changes in behavior or local field potential activity for both control and ataxic mice. These results appear to demonstrate that animal behavior and motor cortical activity are highly correlated. This change can be explained by the alteration of cerebellar Purkinje cells morphology that is observed in spinocerebellar ataxia type 11. To better our understanding of how alterations of Purkinje cell morphology and synaptic properties affect function, a computational neuronal model was used. The results of this model show that decreased dendritic arborization and loss of metabotropic glutamate receptor 1 cause a decrease in firing rate of the Purkinje cell model. Future studies examining activity of the deep cerebellar nuclei and motor thalamus during animal behavior would help to further elucidate how cerebellar output affects the cerebellothalamocortical pathway subsequent animal behavior.

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