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 Mg2+ 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 Mg2+ 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.
Moser
Jochen
J
Institute of Physiology and Pathophysiology, Johannes-Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
Kilb
Werner
W
Werhahn
Konrad-J
KJ
Luhmann
Heiko J
HJ
D000200:Action Potentials / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D004594:Electrophysiology; D004827:Epilepsy / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D008032:Limbic System / Q000254:growth & development / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000378:metabolism; D009924:Organ Culture Techniques; D018709:Statistics, Nonparametric
D008274:Magnesium