The dentate gyrus: a model system for studies of neurotrophin regulation

Studies of the hippocampal formation have demonstrated that seizure activity stimulates a complex pattern of changes in gene expression in differentiated adult neurons including alterations in levels of mRNAs encoding putative neurotransmitter/neuromodulator substances and neurotransmitter receptors. Thus, activity-dependent alterations in gene expression can be expected to effect transient changes in synaptic physiology by modification of both presynaptic and postsynaptic constituents. In work to be reviewed here, seizure paradigms have been utilized to study the influence of activity on the expression of the nerve growth factor (NGF) family of neurotrophins by the dentate gyrus granule cells. We have found that seizures increase the expression of mRNAs for NGF and brain-derived neurotrophic factor (BDNF) but cause a delayed decrease in levels of mRNA for neurotrophin-3 (NT-3) in the granule cells of the dentate gyrus. Differences in the time courses of neurotrophin induction by seizure suggest that multiple regulatory mechanisms are involved. These findings indicate that physiological activity differentially regulates the expression of the three neurotrophins within individual adult forebrain neurons. Moreover, the induction of neurotrophin expression by seizure suggests a mechanism by which epileptiform activity might leave an enduring trace in the functional and structural properties of forebrain circuits which might influence the susceptibility for further seizure activity.