Date of Award

5-2024

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Huo Lu, MD, Ph.D.

Second Advisor

Richard White

Third Advisor

Francis E Jenney, Jr

Fourth Advisor

Brian DeHaven

Abstract

The cerebellum plays an essential role in movement coordination and balance, and its cortex comprises three layers: the granule cell layer, Purkinje cell layer, and molecular layer. The axons of granule cells, parallel fibers, synapse onto the dendrites of the Purkinje cell. Purkinje cells are the primary inhibitory output of the cerebellar cortex to the deep cerebellar nuclei. Damage to the cerebellum or the related pathway can lead to cerebellar ataxia. Cerebellar ataxia can include abnormal extremity movements, eye and gait incoordination, and loss of balance. Non-invasive brain therapy, transcranial direct current stimulation (DCS), has shown potential benefit to patients with ataxia. However, the physiological basis of this therapy still remains unknown. This study aims to understand the effects of DCS on Purkinje cells, providing insights into DCS effects on Purkinje cells, both in normal and ataxic conditions. Other studies suggested that DCS affected the long-term potentiation (LTP) of the CA1 neurons. In the cerebellum, long-term depression (LTD) of the Purkinje cells is considered a more critical cellular mechanism in comparison with LTP for many cerebellar functions. In this study, we will quantitatively measure the effects of DCS at a cellular level in rat pups. The Purkinje cell plasticity was induced with and without applied E-field. Tetanus stimulation was delivered in the molecular layer to induce LTD. E-field was applied onto the cerebellar slice during the recording of a Purkinje cell. The results are expected to demonstrate whether the LTD is enhanced by the DCS. Once we have determined the effects of DCS on LTD, it will provide guidance to our modeling work to simulate the DCS effects in Purkinje cells. Lucifer Yellow will be injected into the recorded cell to verify if there is damage to the morphology of the Purkinje cell.

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