Abstracts

Rationale: Previous studies in vitro suggested that the inhibitory transmission in CA3 layer of rat hippocampus is impaired following repeated neonatal seizures induced by flurothyl. However, little is known on the effect of neonatal seizures on neocortex function. Here we studied the effects of neonatal seizures on spontaneous and miniature inhibitory neurotransmission in somatosensory neocortex. Methods: Sixteen Sprague-Dawley rats were used throughout the study. Rats had 58-60 flurothyl seizures from P1 to P10 and then studied at P20-P30 and compared to age-equivalent controls. Spontaneous and miniature inhibitory postsynaptic currents were recorded using whole-cell patch-clamp technique from pyramidal neurons of layer II in slices of the rat somatosensory cortex. Results: We found that recurrent flurothyl-induced seizures resulted in a marked reduction in GABAergic inhibition in neocortical neurons, as shown by a highly significant decrease in amplitude of spontaneous GABA inhibitory postsynaptic currents. As in the previous work on hippocampal CA3 pyramidal neurons there were no alteration of frequency and kinetic parameters of spontaneous inhibitory postsynaptic currents. Also the frequency, amplitude, rise time and half-width of miniature inhibitory postsynaptic currents, recorded in the presence of TTX, were not modified by neonatal seizures. Conclusions: Our results indicate that alterations of GABA signaling after flurothyl evoked neonatal seizures in neocortex was in the same direction as in the CA3 pyramidal cells of hippocampus. That fact that no reduction in miniature GABA inhibitory postsynaptic currents amplitude and frequency was observed, indicates that the depressing effect of neonatal seizures on spontaneous GABA inhibitory postsynaptic currents in neocortical neurons was not due to a reduced postsynaptic sensitivity to GABA but to a presynaptic depression of GABA release. (Supported by NIH (NINDS) NS041595)