Neurogenesis and Epilepsy

Persistent neural stem cells in the subgranular zone of the hippocampal dentate gyrus generate dentate granule cells (DGCs) throughout life. Many adult-born DGCs integrate into the pre-existing circuitry and acquire electrophysiological characteristics of mature DGCs. Mounting evidence implicates DGC neurogenesis in certain forms of hippocampus-dependent learning and memory and in the modulation of emotional behavior or anxiety. Data from rodent models of medial temporal lobe epilepsy (mTLE) show that prolonged seizures acutely increase adult DGC neurogenesis, but the functional implications of altered neurogenesis in mTLE are poorly understood. Accumulating evidence suggests, however, that altered neurogenesis contributes to several well-characterized cellular abnormalities seen in experimental, and probably human, mTLE. These abnormalities include mossy fiber sprouting, DGC layer dispersion, and the appearance of DGCs in ectopic locations or with abnormal hilar basal dendrites. In contrast, other work suggests that adult-born DGCs that integrate normally during epileptogenesis may serve a compensatory role to restore inhibition. Current work aims to define the mechanisms by which epileptogenic insults alter adult neurogenesis, and whether restoring normal neural stem cell behavior after such insults will attenuate the development of epilepsy or its co-morbidities.