Early developmental alterations of low-Mg2+-induced epileptiform activity in the intact corticohippocampal formation of the newborn mouse in vitro

The generation, propagation and pharmacological properties of low-Mg2+-induced epileptiform activity were examined in the intact corticohippocampal formation (CHF) of the newborn (P0-4) mouse in vitro. Multi-site field potential recordings in dentate gyrus (DG), CA3, CA1, entorhinal cortex (EC) and temporal cortex (TC) revealed in 0.2 mM Mg2+ containing ACSF a stable pattern of spontaneous epileptiform. activity consisting of recurrent ictal-like events (ILEs) and interictal events (IEs). Although this activity could be consistently observed as early as P0, ILES were smaller in amplitude, less frequent and showed a slower onset in P0-2 as compared to P3-4 animals. In all age groups, epileptiform events were largest in CA3 and smallest in EC and TC. A specific pacemaker region could not be identified since ILES appeared simultaneously at all recording sites. Reducing the extracellular Me, concentration to 0.1 mM or nominally zero caused an increase in ILE frequency. Pharmacological studies in the P3-4 age group with 0.2 mM Me, revealed a complete blockade of the ILEs by an NMDA receptor antagonist and a pronounced suppression of epileptiform activity by an AMPA/kainate antagonist. Application of a GABA-A receptor antagonist induced repetitive bursts of interictal discharges, which persisted for at least 1.5 h after washout of the antagonist. Our data demonstrate that the intact CHF in vitro preparation of the newborn mouse offers a most valuable model to study epileptiform. activity in the immature limbic system. (C) 2006 Elsevier B.V. All rights reserved.