Nature Medicine
3, 990 - 996 (1997)
doi:10.1038/nm0997-990
Lesion-induced axonal sprouting and hyperexcitability in the hippocampus in vitro: Implications for the genesis of posttraumatic epilepsyR. Anne Mckinney, Dominique Debanne, Beat H. Gähwiler
& Scott M. ThompsonBrain Research Institute, University of Zurich, August Forel-Strasse 1, CH-8029 Zurich, Switzerland, Correspondence should be addressed to R.A.M. e-mail: mckinney@hifo.unizh.ch
D.D. present address: Unité de Neurocyberéntique Cellulaire, UPR 9041, 280 Boulevard Saint Marguerite, 13009 Marseilles, France The delayed development of recurring seizures is a common consequence of traumatic head injury; the cause of such epilepsy is unknown. We demonstrate here that transection of the mature axons of CA3 pyramidal cells in hippocampal slice cultures leads to the formation by CA3 pyramidal cells of new axon collaterals that are immunoreactive with the growth-associated protein GAP-43. Individual CA3 cell axons had an elevated number of presynaptic boutons 14 days after the lesion, and dual intracellular recordings revealed an increased probability that any two CA3 pyramidal cells were connected by an excitatory synapse. Lesioned cultures were hyperexcitable and synaptic responses often displayed unusual prolonged polysynaptic components. We thus demonstrate that recurrent axon collaterals are newly sprouted by pyramidal cells as a consequence of axonal injury and suggest that this underlies the development of posttraumatic epilepsy.
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