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The Effect of Optogenetic Manipulation of SS interneurons within Malformed, Epileptogenic Cortex

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.

Identiferoai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-5028
Date01 January 2015
CreatorsEkanem, Nicole
PublisherVCU Scholars Compass
Source SetsVirginia Commonwealth University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rights© The Author

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