Date of Completion


Embargo Period



Randall Walikonis and Daniel Mulkey

Field of Study

Physiology and Neurobiology


Master of Science

Open Access

Open Access


Previous studies have shown that seizure activity in chemically induced mouse models leads to several changes in gene expression. A recent study carried out in a genetic model of voltage-gated sodium channel 1.6 (SCN8A) encephalopathy revealed that the same changes occur in these mice. Here, we used two different genetic mouse models of epileptic encephalopathies to determine whether similar changes of expression occur. To begin, we carried out RNA-sequencing in our voltage-gated potassium channel (Kcnq2) conditional knockout mice and found that several genes highlighted in the previous study including those for glial fibrillary acidic protein (GFAP), vimentin (Vim) and galanin (Gal) were upregulated specifically in the hippocampi of mutants. Both fluorescence in-situ hybridization and immunostaining confirmed this. Next we wanted to determine whether these changes were dependent on mechanism of seizure induction. To do so, we used a mouse model of Dravet syndrome with a voltage-gated sodium channel 1.1 (Scn1a) loss of function mutation in which seizures occur as a result of disinhibition. Surprisingly RNA-sequencing revealed that not all of the same genes were upregulated in these mutant mice. Additionally, those that were upregulated were not as significantly increased as in Kcnq2 conditional knockout mice. These results suggest that changes are either mechanism-specific or activity-dependent. A common change seen in both mouse models was that neuropeptides were upregulated. This may point to some neuropeptides as new therapeutic targets in the treatment of epileptic encephalopathies.

Major Advisor

Anastasios Tzingounis

Available for download on Thursday, August 31, 2028