| Literature DB >> 33658509 |
Zane R Lybrand1,2,3, Sonal Goswami1,2, Jingfei Zhu4, Veronica Jarzabek1,2, Nikolas Merlock1,2, Mahafuza Aktar4, Courtney Smith1,2, Ling Zhang4, Parul Varma1,2, Kyung-Ok Cho5,6, Shaoyu Ge7, Jenny Hsieh8,9.
Abstract
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.Entities:
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Year: 2021 PMID： 33658509 DOI： 10.1038/s41467-021-21649-8
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919