Contributions of Adult-Generated Granule Cells to Hippocampal Pathology in Temporal Lobe Epilepsy: A Neuronal Bestiary.

Abstract

Hippocampal neurogenesis continues throughout life in mammals - including humans. During the development of temporal lobe epilepsy, newly-generated hippocampal granule cells integrate abnormally into the brain. Abnormalities include ectopic localization of newborn cells, de novo formation of abnormal basal dendrites, and disruptions of the apical dendritic tree. Changes in granule cell position and dendritic structure fundamentally alter the types of inputs these cells are able to receive, as well as the relative proportions of remaining inputs. Dendritic abnormalities also create new pathways for recurrent excitation in the hippocampus. These abnormalities are hypothesized to contribute to the development of epilepsy, and may underlie cognitive disorders associated with the disease as well. To test this hypothesis, investigators have used pharmacological and genetic strategies in animal models to alter neurogenesis rates, or ablate the newborn cells outright. While findings are mixed and many unanswered questions remain, numerous studies now demonstrate that ablating newborn granule cells can have disease modifying effects in epilepsy. Taken together, findings provide a strong rationale for continued work to elucidate the role of newborn granule cells in epilepsy: both to understand basic mechanisms underlying the disease, and as a potential novel therapy for epilepsy.