Differential Alterations in Excitatory and Inhibitory Networks Involving Dentate Granule Cells Following Chronic Treatment with Distinct Classes of NMDAR Antagonists in Hippocampal Slice Cultures

摘要

Excessive N-methyl-D-aspartate receptor (NMDAR) activation is thought to contribute to brain diseases including epilepsy. However, we showed previously that electrographic seizures involving dentate granule cells induced by a GABAAR antagonist (BMI, 10 micrometers) or removal of Mg2+ (0 mM) were significantly increased following chronic D-APV treatment and modestly increased following chronic memantine treatment. Conversely BMI- and 0 mM Mg2+- induced seizures were dramatically reduced following chronic Ro25,6981 treatment. The goal of this study was to investigate potential mechanisms underlying the differential effects of distinct classes of NMDAR antagonists on seizures. To accomplish this goal, whole-cell electrophysiological recordings and morphological techniques were utilized to examine changes in synaptic connectivity in granule cells from hippocampal slice cultures treated with different classes of NMDAR antagonists.