Abstracts

Rationale: Seizures in the immature brain can lead to the long-term alteration of excitatory-inhibitory balance which may result in a number of behavioral abnormalities in adulthood. In our recent report, we show that recurrent seizures induced in rats during early development affects the seizure susceptibility of somatosensory cortex. Also we showed a significant alteration of inhibitory and NMDA dependent excitatory postsynaptic transmission in pyramidal cells of Layer 2/3 of somatosensory neocortex. The purpose of the present study was to examine if the flurothyl seizures induced in young animals affect synaptic plasticity in the somatosensory region of neocortex later in life. Methods: Thirty Sprague-Dawley rats were used throughout studies. The volatile agent flurothyl was used to induce seizures. Fifteen rats were exposed to flurothyl five times per day for 15 days beginning at postnatal day (P) 1. Control rats (n=15) were placed in the chamber for equivalent periods of time as the flurothyl-treated rats but were not exposed to flurothyl. Experiments were performed at the postnatal age of 60 to 80. Recordings were made in coronal cortical slices. Extracellular recording electrodes were placed in the L2/3 of the somatosensory neocortex, stimulating electrodes were positioned in the same column but in L5/6. Potentiation of evoked field potentials was induced using prime burst protocol. Results: We show that the conditioning stimulation of L5/6 area of somatosensory cortex induce short-term increase in evoked field potentials in L2/3 area in slices from control rats. This increase lasted no more than twenty minutes. Adding the blocker of inhibitory synaptic transmission gabazine in the recording pipette solution increased the magnitude of potentiation in response to the second and third conditioning stimuli in control slices. However, the potentiation observed in control slices in the presence of gabazine rapidly declined after the third conditioning stimuli with only a 10% increase of field potential amplitudes observed after 40 minutes. In slices from flurothyl exposed rats we observed prolonged increase in amplitude of field potentials in response to the conditioning stimulation. In the condition when inhibitory synaptic transmission was blocked conditioning stimulation evoked increases magnitude of field potential in slices from flurothyl treated rats to the same value as for control slices. However, the duration of potentiation significantly increased comparatively to control slices. Conclusions: Our findings demonstrate that seizures induced by flurothyl early in development have a long-term effect on the plasticity of somatosensory cortex (Sponsored by NIH NINDS grant numbers: NS041595).