Dual role of GABA in the neonatal rat hippocampus

The effects of modulators of GABA-A receptors on neuronal network activity were studied in the neonatal (postnatal days 0-5) rat hippocampus in vitro. Under control conditions, the physiological pattern of activity of the neo natal hippocampal network was characterized by spontaneous network-driven g iant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacin e (1-2 mu M) and the allosteric modulator diazepam (2 mu M) induced biphasi c responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GAB A-A receptor antagonists bicuculline (10 mu M) and picrotoxin (100 mu M) bl ocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interict al- and ictal-like activities in the hippocampal slices and the intact hipp ocampus. These data suggest that at early postnatal ages GABA can exert a d ual - both excitatory and inhibitory - action on the network activity. Copy right (C) 1999 S. Karger AG, Basel.