The Developmental Stage of Dentate Granule Cells Dictates Their Contribution to Seizure-Induced Plasticity

By M. Kron, Helen Zhang, J. Parent. 2010

198 citations recorded by the source corpus.

Dentate granule cell (DGC) neurogenesis persists throughout life in the hippocampal dentate gyrus. In rodent temporal lobe epilepsy models, status epilepticus (SE) stimulates neurogenesis, but many newborn DGCs integrate aberrantly and are hyperexcitable, whereas others may integrate normally and restore inhibition. The overall influence of altered neurogenesis on epileptogenesis is therefore unclear. To better understand the role DGC neurogenesis plays in seizure-induced plasticity, we injected retroviral (RV) reporters to label dividing DGC progenitors at specific times before or after SE, or used x-irradiation to suppress neurogenesis. RV injections 7 weeks before SE to mark DGCs that had matured by the time of SE labeled cells with normal placement and morphology 4 weeks after SE. RV injections 2 or 4 weeks before seizure induction to label cells still developing during SE revealed normally located DGCs exhibiting hilar basal dendrites and mossy fiber sprouting (MFS) when observed 4 weeks after SE. Cells labeled by injecting RV after SE displayed hilar basal dendrites and ectopic migration, but not sprouting, at 28 d after SE; when examined 10 weeks after SE, however, these cells showed robust MFS. Eliminating cohorts of newborn DGCs by focal brain irradiation at specific times before or after SE decreased MFS or hilar ectopic DGCs, supporting the RV labeling results. These findings indicate that developing DGCs exhibit maturation-dependent vulnerability to SE, indicating that abnormal DGC plasticity derives exclusively from aberrantly developing DGCs. Treatments that restore normal DGC development after epileptogenic insults may therefore ameliorate epileptogenic network dysfunction and associated morbidities.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Developmental Neuroscience

In Molecular Biology

Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “For example, seizure-induced SGZ neurogenesis may contribute to epileptogenesis and long-term cognitive impairment (Jessberger et al., 2007; Kron et al., 2010).”
Extended interneuronal network of the dentate gyrus (2017, methodology): “We injected Syn-GTR bilaterally into the dorsal dentate gyrus at postnatal day (P) 7 as previously described (Althaus et al., 2016; Kron et al., 2010) to birthdate neonatally-born dentate granule cells and render them RbV-competent.”
Adult neurogenesis and the plasticity of the dentate gyrus network (2011, background): “…in DISC1 loss of function (Duan et al., 2007) or toward the hilus after epileptic seizures (Scharfman et al., 2003; Jessberger et al., 2007; Kron et al., 2010) indicates that newborn DGCs do have the potential to migrate further away from the subgranular zone and in both directions, but…”