A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 03, 2021
- Source ID
- 10.1038/s41467-021-21649-8
Entities
People
- Courtney Smith
- Jenny Hsieh
- Jingfei Zhu
- Kyung-Ok Cho
- Ling Zhang
- Mahafuza Aktar
- Nikolas Merlock
- Parul Varma
- Shaoyu Ge
- Sonal Goswami
- Veronica Jarzabek
- Zane R. Lybrand
Organizations
- Center for Scientific Review
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging
- Robert J Kleberg Jr and Helen C Kleberg Foundation
- United States Department of Defense
- United States Department of Health and Human Services