Abstracts

It has been shown that neonatal seizures can lead to long-term consequences including alteration of seizure susceptibility and impairment in spatial memory. During the first weeks of life there are dramatic changes in synaptic function in the brain including an increasing number of synapses, decreasing number of silent pure NMDA-based synapses, changes in the subunit composition of NMDA receptors, and a transition from GABA-induced depolarization to a hyperpolarizing effect. Little is known about the effects of neonatal seizures on development changes occurring in synaptic transmission during the first postnatal weeks. The purpose of present study is to examine the effect of flurothyl-induced seizures on inhibitory and excitatory synaptic transmission of the developing rat hippocampus. Twenty-eight Sprague-Dawley rats were used throughout experiments. The volatile agent flurothyl was used to induce seizures. Fifteen rats were exposed to convulsant doses of flurothyl 5 times per day for 5 days beginning at postnatal day (P) 1. Control rats ([italic]n[/italic]=13) were placed in the chamber for equivalent periods of time as the flurothyl-treated rats but were not exposed to flurothyl. Whole-cell patch clamp recordings were made from the hippocampal CA3 region in slice preparations 3-11 days after the last seizure (age P8[ndash]P17) from both control and flurothyl-treated rats. In control slices the amplitude and frequency of NMDA and AMPA spontaneous excitatory postsynaptic currents (sEPSCs) significantly increased over the second and third postnatal weeks and the kinetics of decay of NMDA sEPSC shortened from 56.5 [plusmn] 4.8 ms at P8-10 to 22.9 [plusmn] 1.8 ms by P15[ndash]P17. We also found that recurrent neonatal seizures induced between P1-P5 did not alter developmental changes of the excitatory transmission system after the flurothyl-evoked seizures. Neonatal seizures did not alter the ratio of AMPA/NMDA sEPSCs relationship in regard to either frequency or amplitude. We also analyzed the amplitude and frequency of GABA spontaneous excitatory postsynaptic currents (sEPSCs). The frequency and amplitude of sIPSCs in control rats increased significantly during the second and third postnatal weeks. While the developmental changes of frequency of GABA-mediated spontaneous inhibitory postsynaptic currents (sIPSC) was not modified by neonatal seizures, the amplitude of sIPSCs in P15-17 flurothyl-treated rats was significantly decreased comparatively to seizure na[Iuml]ve rats. Our findings demonstrate that neonatal seizures are associated with a reduction in the amplitude of GABA-mediated currents. These changes were noted days after the last seizure and may have long-term effects on brain excitability. (Supported by the NINDS (R01NS041595).)