Epilepsy is associated with significant neurological morbidity, including
learning disabilities, motor deficits, and behavioral problems. Although the causes of neurological dysfunction in
epilepsy are multifactorial, accumulating evidence indicates that
seizures in themselves may directly cause
brain injury. Although it is clear that
seizures can result in neuronal death, it is likely that under some circumstances
seizures can induce more subtle functional or structural alterations in neurons. We induced focal neocortical
seizures with
4-aminopyridine in transgenic mice expressing
green fluorescent protein in cortical neurons and sequentially imaged individual dendrites in living animals with two-photon
laser-scanning microscopy to determine whether these
seizures caused acute alterations in dendritic spine morphology. No dendritic alterations were observed in anesthetized animals during electrographic
seizures over a 3-hour period. Similarly, in unanesthetized mice, low-stage, clinical electrographic
seizures had minimal effect on dendritic spines. More severe, high-stage
seizures in unanesthetized mice were associated with a moderate loss of spines and dendritic swelling, but this effect may have been contingent on a synergistic action of
phototoxicity from the imaging method itself. Overall, our results suggest that most neocortical
seizures have minimal acute effects on dendrites over several hours, but may predispose to dendritic injury under extreme conditions.