GRANULE CELLS

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 ectopic 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 excitability while promoting synchronized discharge in response to certain types of afferent excitation. Outstanding issues with regard to the role of dentate granule cells in epileptogenicity include the possibility of additional alterations in intrinsic and synaptic properties of these cells, as well as the impact of these cellular and circuit changes on cognitive ability and the requirements for seizure propagation through the dentate gyrus. Issues specific to ectopic granule cells include the mechanisms that enable them to retain the hyperexcitable phenotype of immature granule cells and that contribute to their spontaneous bursting.

Duke Scholars

Author J. Victor Nadler Pharmacology & Cancer Biology