Abstracts

Rationale: Dysregulated hippocampal neurogenesis is a prominent feature of temporal lobe epilepsy (TLE). Anatomical data indicate that most dentate granule cells (DGCs) generated in response to an epileptic insult develop features that promote increased excitability, including ectopic location, persistent hilar basal dendrites (HBDs) and mossy fiber sprouting. However, some DGCs appear to integrate normally, and may promote reduced excitability. Using a retroviral (RV) GFP reporter to birthdate DGCs, our laboratory found that DGCs that were mature at status epilepticus (SE) are resistant to morphological abnormalities, while the majority of those born after SE display TLE-related pathology. This may suggest that post-SE generated DGCs promote pathological function while established DGCs retain normal function.Methods: To examine the relationship between DGC age and activity within an epileptic network, we used acutely prepared hippocampal slices to make whole-cell voltage clamp recordings from RV birth-dated DGCs born either neonatally, or during adulthood in an epileptic or intact animal.Results: We found that, in TLE tissues, both adult-born and neonatal-born populations of DGCs appear to receive increased excitatory input compared with age-matched controls in intact tissues. Furthermore, adult-born DGCs that display aberrant morphology in TLE tissues appear to receive more excitatory input than their normotopic counterparts. In particular, ectopic DGCs receive the greatest amount of excitatory input and least amount of inhibitory input when compared to other age and morphology defined groups of DGCs. Taken together, these data suggest that aberrant adult-born DGCs may underlie pathophysiological network mechanisms that promote epileptogensis.Conclusions: Taken together, these data suggest that aberrant adult-born DGCs may underlie pathophysiological network mechanisms that promote epileptogensis.