Effects of chronic network hyperexcitability on the growth of hippocampal dendrites

Experiments reported here were motivated by studies in both human epilepsy and animal models in which stunted dendritic arbors are observed. Our goal was to determine if chronic network hyperexcitability alters dendritic growth. Experiments were conducted in hippocampal slice cultures obtained from infant mice that express the fluorescent protein YFP in CA1 hippocampal pyramidal cells. Results showed that 4 days of GABAa receptor blockade produced a 40% decrease in basilar dendritic length. When dendritic growth was followed over this 4-day interval, dendrites in untreated slices doubled in length, however dendrites in bicuculline treated cultures failed to grow. These effects were suppressed by APV - suggesting a dependence on NMDA receptor activation. Activation of the transcription factor CREB was also decreased by chronic network hyperexcitability - pointing to possible molecular events underlying the observed suppression of growth. Taken together, our results suggest that chronic hippocampal network hyperexcitability limits dendritic growth.