Properties of dentate granule cells and their relevance to seizures
Encoding into declarative memory of the distinct temporal and spatial relationships comprising events depends on the activity of dentate granule cells. This component of memory formation is referred to as pattern separation. The same cellular and synaptic properties that subserve pattern separation also allow dentate granule cells to resist the propagation of seizures. Many changes in the innervation and receptor expression of these cells occur during epileptogenesis. In addition, hyperexcitable granule cells are generated and integrate into the dentate gyrus circuitry. The net effect of these changes may be to maintain a low baseline level of circuit excitability while promoting synchronized discharge in response to certain types of afferent excitation. The overall impact of seizure-associated plasticity in the dentate gyrus depends on the balance between changes that promote and inhibit hyperexcitability. This balance may differ in different epilepsy models and under different conditions in the same model, thus possibly explaining seemingly contradictory findings in the literature. Animal studies, on balance, support the development of dentate gyrus-based therapies for temporal lobe epilepsy, but they will need to target specifically those seizure-associated changes that promote hyperexcitability.
