Decrease in inhibition in dentate granule cells from patients with medial temporal lobe epilepsy

Alterations in synaptic inhibition are associated with epileptiform activit y in several acute animal models; however, it is not dear if there are chan ges in inhibition in chronically epileptic tissue. We have used intracellul ar recordings from granule cells of patients with temporal lobe epilepsy to determine whether synaptic inhibition is compromised. Two groups of patien ts with medial temporal lobe epilepsy were used, those with medial temporal lobe sclerosis (MTLE), and those with extrahippocampal masses (MaTLE) wher e the cell loss and synaptic reorganization that characterize MTLE are not seen. Although the level of tonic inhibition at the somata was not signific antly different in the two patient groups, there was a reduction in the con ductance of polysynaptic perforant path-evoked fast and slow inhibitory pos tsynaptic potentials (IPSPs) (53% and 66%, respectively). We found that the re was a comparable decrease in the monosynaptic IPSP conductances examined in the presence of glutamatergic antagonists as that seen for the polysyna ptically evoked IPSPs. These data suggest that the decrease in inhibition s een in normal. artificial cerebrospinal fluid in MTLE granule cells cannot be solely explained by a decrease in excitatory input onto inhibitory inter neurons and may reflect changes at the interneuron-granule cells synapse or in the number of specific inhibitory interneurons.