Carbachol can limit seizure like activity by preferentially enhancing inhibition in rat hippocampus

Epilepsy is characterized by spontaneous and recurrent seizures; the excessive and synchronous firing of neurons generally due to increase in the ratio of excitation to inhibition (E:I). In aged mammals the susceptibility for seizure activity increases with senescence, along with a decrease in cholinergic tone. Here we tested the hypothesis that cholinergic stimulation limits seizures generation by reducing E:I in hippocampal networks. Carbachol (CCh), a parasympathomimetic agent, was bath applied following the induction of seizure-like activity in the CA3 region of rat hippocampal slices. Three models of epilepsy were employed: the low-Mg2+ model which increase excitation and the bicuculline model and picrotoxin models which reduce inhibition. CCh diminished the frequency of spontaneous bursts in the low Mg2+ model. In contrast, it had no significant effect on bicuculline-induced bursts and increased picrotoxin-induced spontaneous burst frequency. Consistent with this hypothesis we found CCh increased paired pulse inhibition in extracellular field recordings and increased firing rates of interneurons. These results suggest cholinergic receptor activation preferentially enhance network synaptic inhibition over excitation.