Ex vivo neocortical transcriptomic changes induced by epileptiform activity in male and female mice

Seizures are often associated with epilepsy; however, they can also be a symptom of many different diseases. Seizures can be brief, lasting approximately 10 seconds, or, in their most severe presentation, they can last many hours. A hallmark of a seizure is that it involves nearly every neuron in the brain region recruited to the event. Many studies have demonstrated that seizures result in large-scale gene transcription changes that invariably alter neuronal function. We have developed an ex vivo technique to probe transcriptional changes induced by seizure-like activity using RNA sequencing from mouse neocortical tissue. We found little difference between the seizure-induced transcriptional changes from male and female brain slices. In addition, we demonstrate that ex vivo seizure induction can mimic the large-scale transcriptional changes seen in in vivo studies, using a simple and reduced model of epilepsy that can be tightly controlled and regulated with pharmacology, optogenetic tools, or chemogenetics. This new model allows for easy manipulation of the cortical network to understand how changing network properties with the aforementioned tools can alter the transcriptional landscape during seizure activity. We propose that simpler models like the one described in this manuscript can be ideal when searching for novel therapies for various disorders.