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 neonatal hippocampal network was characterized by spontaneous network-driven giant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacine (1-2 microM) and the allosteric modulator diazepam (2 microM) induced biphasic responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GABA-A receptor antagonists bicuculline (10 microM) and picrotoxin (100 microM) blocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interictal- and ictal-like activities in the hippocampal slices and the intact hippocampus. These data suggest that at early postnatal ages GABA can exert a dual - both excitatory and inhibitory - action on the network activity.
Khalilov
I
I
INMED, Marseille, France.
Dzhala
V
V
Ben-Ari
Y
Y
Khazipov
R
R
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007539:Isonicotinic Acids / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D007539:Isonicotinic Acids; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D001640:Bicuculline; C015300:isoguvacine