Abstracts

Animal models of temporal lobe epilepsy (TLE) demonstrate loss of layer III neurons in the mEC and marked hyperexcitability in layer II neurons, despite sparing of GABAergic interneurons. Altered GABA[sub]A[/sub] receptor mediated synaptic transmission may contribute to the hyperexcitability observed in mEC Layer II stellate cells. To address this question, we used whole cell recording techniques in combined mEC-HC brain slices obtained from saline-treated and kainic acid (KA)-treated rats to examine the short-term synaptic plasticity of inhibitory postsynaptic currents (eIPSCs) evoked via minimal stimulation in layer II neurons. Male Sprague-Dawley rats (150g) were injected hourly with KA (5 mg/kg, [italic]ip[/italic]) or saline (0.9%) to stage 4/5 seizure activity (Racine, 1972). Whole cell voltage clamp recordings of eIPSCs were recorded from visualized layer II neurons of the mEC in combined mEC-HC ventral brain slices (400[mu]m) at 31[plusmn]1[deg]C. GABA mediated eIPSCs were isolated in oxygenated ACSF containing APV (50[mu]M) and CNQX (10[mu]M). The internal pipette solution contained (in mM): CsGluconate (125), CsCl (10), HEPES (10), EGTA (1), CaCl[sub]2[/sub] (0.5), glucose (10), and QX-314 (5) (pH=7.28; mOsm=290). The short-term synaptic plasticity of eIPSCs were evaluated following paired- and triple-pulse stimulation paradigms (100-200ms interstimulus intervals). In addition, eIPSC peak amplitude ratios were compared following tetanic stimulation (10Hz-20Hz). Paired pulse depression (PPD) of GABAergic eIPSCs in Layer II mEC was detected in slices from both control rats and rats which had undergone KA-induced seizures 1-2 weeks prior: IPSC2/IPSC1 ratio=0.821 [plusmn] 0.02 (KA) vs 0.839 [plusmn] 0.1 (control). In addition, eIPSC peak ampitudes were further depressed in triple-pulse comparisons in mEC Layer II neurons from both control and KA-treated groups: IPSC3/IPSC2 ratio = 0.823 [plusmn] 0.09 (KA) vs 0.823 [plusmn] 0.08 (control). These results suggest that alterations in the probability of release of GABA from presynaptic cells does not contribute to the hyperexcitability observed in Layer II of the mEC after KA-induced seizure activity. Short-term synaptic plasticity in inhibitory circuits is a critical component in the maintenance of balance between excitatory/inhibitory transmission in the mEC-HC circuit. Altered inhibitory synaptic transmission can lead to hyperexcitability by disrupting this balance, potentially facilitating the development and/or spread of seizure activity throughout the temporal lobe. Although Layer II neurons from both control and KA-treated rats showed similar depression of GABAergic postsynaptic currents, characterization of postsynaptic and presynaptic changes taking place during epileptogenesis may provide insight into the hyperexcitability observed in Layer II stellate neurons following KA-induced seizures. (Supported by EFA Postdoctoral Fellowship (MDSY), NS-040049 (HSW), and NS-044210 (KSW).)