Effects of chronic network hyperexcitability on the growth of hippocampal dendrites

Neurobiol Dis. 2008 Feb;29(2):267-77. doi: 10.1016/j.nbd.2007.08.018. Epub 2007 Sep 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Bicuculline / pharmacology
  • CREB-Binding Protein / metabolism
  • Convulsants / pharmacology
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Dendrites / ultrastructure
  • Drug Interactions
  • Hippocampus / cytology*
  • Hippocampus / drug effects
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Thy-1 Antigens / genetics
  • Valine / analogs & derivatives
  • Valine / pharmacology


  • Convulsants
  • Luminescent Proteins
  • Thy-1 Antigens
  • 2-amino-5-phosphopentanoic acid
  • CREB-Binding Protein
  • Valine
  • Bicuculline