Early-life seizure sensitive neurones: Their characteristics and role in epilepsy pathology

There is a large body of literature exploring early-life-seizures (ELS), however, much of this research focuses on whole brain regions. This thesis aims to understand the characteristics of ELS-sensitive neurones and their role in future seizure pathology. Using c-Fos-GFP/c-Fos-tTA based transgenic mice, we found that at P10 ~18% of pyramidal neurones are activated in the CA1 pyramidal layer of the hippocampus in response to a kainic acid (KA) seizure. Electrophysiology recordings of ELS-sensitive neurones found a decrease in spontaneous GABA activity. Using c-Fos-GFP/c-Fos-tTA/TRE-hM3Dq mice, which flags ELS-sensitive neurones with the excitatory DREADD hM3Dq, we found that reactivating ELS-sensitive neurones is sufficient to evoke seizures. Finally, using c-Fos-GFP/c-Fos-tTA/TRE-hM4Di mice with the inhibitory DREADD hM4Di, we found that suppressing ELS-sensitive neurones after a seizure recovers the increase in excitability. These results indicate that ELS-sensitive neurones play a crucial role in future seizure pathology and pose a unique target for further research.