A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy

In the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to local inhibitory feedback circuitry, whether they are involved in epileptogenesis remains elusive. Here, we identify a critical window of activity associated with the aberrant maturation of abGCs characterized by abnormal dendrite morphology, ectopic migration, and SRS. Importantly, in a mouse model of temporal lobe epilepsy, silencing aberrant abGCs during this critical period reduces abnormal dendrite morphology, cell migration, and SRS. Using mono-synaptic tracers, we show silencing aberrant abGCs decreases recurrent CA3 back-projections and restores proper cortical connections to the hippocampus. Furthermore, we show that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity. Our results demonstrate that aberrant neurogenesis rewires hippocampal circuitry aggravating epilepsy in mice. Adult-born granule cells integrate in hippocampal circuitry and contribute to hippocampal function. Here, the authors show that a critical period of neuronal activity regulates aberrant neurogenesis to rewire hippocampal circuitry and drive seizures in a mouse model of epilepsy.

Automated summary

In this study, researchers identified a critical window of activity associated with the aberrant maturation of adult-born granule cells (abGCs) in the mammalian hippocampus, which contributes to epileptogenesis. Silencing aberrant abGCs during this critical period reduced abnormal dendrite morphology, cell migration, and seizures in a mouse model of temporal lobe epilepsy. Furthermore, the study demonstrated that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity.