Date of Award
Doctor of Philosophy (PhD)
Epilepsy is associated with a very high incidence of cognitive and behavioral comorbidities that are detrimental to overall quality of life. Current treatments for epilepsy,namely anticonvulsant pharmacological agents, generally increase the amount of inhibitory drive in order to counteract the hyperexcitability observed in the disorder. However, administration of these agents, while effective for 70% of epilepsy sufferers, leave a residual 30% of patients who don’t become seizure-free. The concomitant adverse side effects of anticonvulsants - these can paradoxically include increased cognitive "fog" or confusion, automatisms, and even increased number of seizures - are a great additional concern, as is the etiology, that is, the damage, responsible for the disorders in the first place. These considerations, therefore, indicate a need for novel treatment approaches to target both seizures and cognition. Previous and ongoing research indicates a more complex story than the excitation/inhibition imbalance that has become typical. Rather, specific patterns of neuronal loss and synaptic reorganization are believed to lead to modifications in the firing properties of surviving neurons. Interneurons, through variegated patterns of connectivity and physiology, are critical for temporally regulating the firing of neuronal networks. Through the implantation of interneuron progenitor cells obtained from the medial ganglionic eminence (MGE), we investigated changes in cognitive outcome and performance on tasks of spatial working memory. We found that epileptic rodents receiving grafts of MGE-derived progenitor cells in the dorsal hippocampus performed better on the Morris Water Maze, a task of spatial navigation and cognition, when compared to animals receiving only vehicle injections. Additionally, in vivo local field potential and single-unit recordings in CA1 of the hippocampus revealed differences in firing parameters between experimental groups, indicating modification of rate and temporal coding of host cells by progenitors. These encouraging results will be further explored in future studies.
Number of Pages
Curry, Willie, "The effects of interneuron progenitor cell transplantation on network dynamics in an animal model of mesial temporal lobe epilepsy" (2021). Graduate College Dissertations and Theses. 1440.