DOI
https://doi.org/10.25772/VMMK-5138
Defense Date
2015
Document Type
Thesis
Degree Name
Master of Science
Department
Anatomy & Neurobiology
First Advisor
Kimberle Jacobs
Second Advisor
Thomas Reeves
Third Advisor
Stacey Reynolds
Abstract
A large percentage of individuals with intractable epilepsies have an accompanying cortical malformation, the underlying cellular mechanisms of which are poorly understood. It is known however that in an animal model for one such malformation, polymicrogyria, epileptogenesis occurs most easily from an adjacent area termed the paramicrogyral region (PMR). Previous studies implicate SS interneurons as a potential contributor to this pathology, which lead to our hypothesis: in PMR, SS interneurons exert a higher modulatory influence on excitatory pyramidal cells, as compared to the same by SS interneurons within homologous control cortex.
Using a freeze-lesion model for polymicrogyria in transgenic mice that selectively express either Channelrhodopsin or Archaerhodopsin optogenetic channels in these cells, we assessed the contribution of SS interneurons as it potentially differs between layer V of PMR and control cortex. These studies provided the following biological examples in support of previous extrapolations that indicate SS over-activation within PMR: (1) SS interneuron mediated evocation of inhibitory events in layer V excitatory neurons is more robust in PMR than in control. Similarly, electrically-evoked inhibitory events in these excitatory neurons trend towards being larger, signifying a larger contribution by interneurons. (2) SS interneuron mediated suppression of electrically-evoked responses trends towards being stronger in PMR; and (3) the selective silencing of SS interneurons might not impart an effect on spontaneous inhibitory postsynaptic events.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-21-2015