DOI
https://doi.org/10.25772/8CQH-SK35
Defense Date
2016
Document Type
Thesis
Degree Name
Master of Science
Department
Anatomy & Neurobiology
First Advisor
Dr. Kimberle Jacobs
Second Advisor
Dr. John Bigbee
Third Advisor
Dr. Jamie Sturgill
Abstract
Epilepsy has been previously attributed to either increased excitation or decreased inhibition. With this closed frame of mind, modern medicine has been unable to develop a permanent treatment against the mechanisms of epilepsy. In order to treat patients with intractable seizures, especially those caused by developmental malformations, it is essential to understand the entirety of mechanisms that could possibly play a role in the abnormal cortical function. One such developmental malformation is known as polymicrogyria. Epileptogenesis occurs in an area laterally adjacent to this malformation known as the paramicrogyral region (PMR). Past studies have narrowed down the potential cause of this increased network excitation to a certain type of inhibitory interneuron, the somatostatin (SS) interneuron. Additionally, previous studies have shown an increase in the mGlu5 receptor on this interneurons in the PMR region only and not in control tissue, meaning that targeting these receptors as treatment will not affect normal functioning tissue. These results lead to our hypothesis: blockade of the mGluRs will decrease the 2 activity of SS interneurons and thereby prevent the generation of epileptiform activity and increased SS output in malformed cortex. Utilizing the freeze-lesion model for microgyria in transgenic mice expressing Channelrhodopsin optogenetic channels in SS interneurons, we assessed the contribution of these SS interneurons in four different animal groups: control or PMR treated with either Gabapentin, a current AED (antiepileptic drug), or MTEP, an mGlu5 receptor antagonist. We tested the effects of these two drugs on SS interneuron output to determine whether they decrease the over activation in the PMR that has been previously studied. The following study revealed no correlation between Gabapentin-treated animals and a decrease in epileptiform activity. Additionally, no significant difference was seen between the MTEP-treated groups in the protocols that were measured.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-2-2016