SUPPRESSION OF SYNAPTOGENESIS BY EPILEPTIFORM DISCHARGES IN HIPPOCAMPAL SLICE CULTURE

Using an organotypic slice culture of the hippocampus, the effects of epileptic activities on synapse reorganization following axotomy were investigated. The maximal amplitude of field excitatory postsynaptic p otentials that reflected the number of functional synaptic contacts we re recorded 7 d after the mossy fibers or Schaffer collaterals were tr ansected at 8 d in vitro. Fifty mu M picrotoxin elicited epileptiform bursts, whose severity in the CA1 region was loner than that in the CA 3 region. Synapse reformation of the mossy fibers was significantly pr evented by picrotoxin, and that of Schaffer collaterals also tended to be attenuated. Ten mu M bicuculline, 1 mM pentylenetetrazol or 2 mM 4 -aminopyridine also induced epileptic activities in the CA3 region and significantly depressed synapse formation of the mossy fibers. Using cultures of dispersed neurons, eve found that the prolonged depolariza tion of membrane potentials promoted neurite outgrowth. Taken together , we concluded that the preventing effects of epileptic activities on synapse reorganization following axotomy was due to the inhibition of the synaptogenesis process, not to a blockade of axon outgrowth.