DOI
https://doi.org/10.25772/SMGT-8T59
Defense Date
2023
Document Type
Thesis
Degree Name
Master of Science
Department
Anatomy & Neurobiology
First Advisor
Kimberle M Jacobs
Second Advisor
Carmen Sato-Bigbee
Third Advisor
John Bigbee
Abstract
A large percentage of individuals with intractable epilepsies have an accompanying cortical malformation, the underlying cellular mechanisms of which are not fully understood. In an animal model for one such malformation, polymicrogyria, epileptogenesis occurs most easily in a region of tissue just adjacent to the microgyria termed the paramicrogyral region (PMR). Previous studies implicate somatostatin containing interneurons (SOM) as a potential contributor to this pathology, and show increased excitation of SOM in the PMR. We hypothesis that SOM are more active in the PMR when compared to SOM within the homologous region of the control cortex. In addition to this parvalbumin containing interneurons (PV) are less active than SOM in the PMR.
Using a freeze-lesion model for polymicrogyria in transgenic mice that express green fluorescent protein (GFP) under the control of the cFOS promoter we assessed the activity levels of SOM and PV in the PMR and control cortex. A Kainic Acid (KA) injection was used to induce a seizure in the mice. The difference in activity levels of SOM and PV were measured with and without KA injection. These studies did not support our hypothesis. The measured activity of the cortex, as assayed by GFP expression, did not change in the PMR when compared to a control cortex, even after KA injection. In contrast to previous findings the population of PV did not decrease in the PMR when compared to a homologous region in a control cortex. SOM were more active than PV across subject group and condition. Both interneuron populations were found to be less active after KA injection.
The lack of change in cortical activity is due to a high signal to noise ratio which was produced by not suppressing the social and neural activity of the mice before they were perfused by socially isolating the animals for 1-7 days before perfusing, and perfusing the mice before peak protein expression, which occurs 90 minutes after the stimulation of neural activity. The decrease in PV population has been observed in layer V, this investigation imaged the whole somatosensory cortex not just layer V, any change in neuronal population in layer V was masked by imaging a larger sample of the cortex. SOM were more active than PV across subject group and condition, this stands in contrast to the mixed evidence in the literature that PV has a higher spontaneous firing rate than SOM. The reduced activity in PV interneurons is in line with our hypothesis that SOM disinhibit pyramidal cells by inhibiting the activity of PV during the onset of a seizure. The reduced activity of SOM in this model is believed to be a product of SOM’s sensitivity to excitotoxicity in the cortex and a product of SOM experiencing depolarization block coincident with ictal activity in pyramidal cells.
Rights
© Peter Francis Lamothe
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-11-2023