Analysis of differences in hippocampal adult neurogenesis induced by acute mild and severe seizures in young mice

Adult hippocampal neurogenesis (AHN) occurs in the subgranular zone (SGZ) of the dentate gyrus (DG) in mice and can be modulated by events such as hyperexcitability present in epilepsy. Evidence shows increased aberrant AHN in chronic severe epilepsy models; however, the impact of mild seizures remains to be explored. In this study, we administered intraperitoneally a low (5mg/kg) or a high dose (25 mg/kg) of kainic acid (KA) to Ascl1/Tom young mice (6-8 weeks) that allow us to target new neurons, to induce acute mild or acute severe seizures, respectively and evaluate differences in neurons born under these two hyperexcitability conditions. Our findings reveal a lower number of Tom+ neurons born in the mild condition (MC), whereas the severe condition (SC) associated to increased neuron proliferation. Migration patterns show that in the MC, newborn neurons are located near the SGZ, as in the control group. In contrast, in the SC an atypical distribution of Ascl1+ cells within the granular cell layer and ectopic cells in the hilus were observed; cell phenotype remained unchanged. We assessed the performance of subjects in hippocampal and neurogenesis-dependent tasks such as object localization (OLM) and contextual fear memory (CFM) respectively. Performance in CFM is not affected between conditions; however, OLM is affected in both conditions compared to the control group. Our results suggest that maturation of newborn neurons depend on the severity of hyperexcitability and concomitant seizures, suggesting that neurons born under pathological conditions may differentially influence hippocampal circuitry and its related behavior.