Enhanced endogenous activation of NMDA receptors in pyramidal neurons of hippocampal tissues from patients with mesial temporal lobe epilepsy: A mechanism of hyper excitation

Abstract

Altered excitatory synaptic transmission is one of the primary causes of seizure generation in patients with mesial temporal lobe epilepsy (MTLE). The present study is designed to delineate the contribution of glutamatergic tone under resting conditions to the hyper excitability in patients with MTLE. Resected hippocampal tissues were obtained from patients with MTLE. In these samples spontaneous excitatory postsynaptic currents (EPSCs), sensitive to NMDA receptor antagonist APV (50μM) and AMPA receptor antagonist CNQX (10μM) were recorded from pyramidal neurons at −70mV. We observed that frequency of EPSCs were 28.2% higher in slices obtained from patients with MTLE compared to that in case of non-epileptic controls. We also examined spontaneous fast current transients (CTs) recorded from these pyramidal neurons under cell-attached configuration. The frequency of CTs increased in the absence of extracellular Mg2+ in brain slice preparations and was completely blocked by APV. We found that the frequency of CTs in pyramidal neurons were higher in case of MTLE samples compared to non-epileptic controls. This study suggests that enhanced endogenous activity of NMDA receptor contributes to excitability in pyramidal neurons of slice preparations obtained from patients with MTLE.