Reduction of postsynaptic inhibition tolerated before seizure initiation: brain stem.

The reduction of GABA-mediated postsynaptic inhibition tolerated before seizure initiation was assessed using the GABA-mediated, disynaptic, inhibitory pathway from the ipsilateral vestibular nerve to trochlear motoneurons in pentobarbital-anesthetized cats. The amplitude of intracellularly recorded IPSPs or the corresponding extracellular field potential was monitored while incremental doses of the specific GABA antagonist, bicuculline, were injected intravenously. Cortical seizures (measured by ECoG activity) and spontaneous trochlear motoneuron bursting occurred at bicuculline doses which reduced inhibitory vestibular-trochlear field potentials by 10% or less. After midbrain transection trochlear motoneurons no longer participated in the cortical seizures. Rather, a widespread, paroxysmal increase of intrinsic brain stem activity, including motoneuron bursting, occurred after injection of additional bicuculline sufficient to reduce the vestibular-trochlear inhibition to 25% of control or less. Thus, postsynaptic inhibition could be virtually eliminated before intrinsic brain stem seizures were triggered, but the brain stem could participate in cortical seizures in spite of the integrity of inhibitory brain stem pathways. Because the cortex seized when inhibitory potentials were only slightly reduced in the brain stem, we suggest that factors such as different GABA receptor properties or altered membrane properties may contribute to the greater sensitivity of cortex to bicuculline.