GABAA- and GABAB-mediated inhibition in the rat dentate gyrus in vitro.
Many studies suggest that the dentate gyrus (DG) is a control point for hippocampal epileptogenesis. However, the importance of GABAergic inhibition in the DG is not quite clear. Intracellular recordings were obtained from granule cells (GC) of the rat DG. In addition to GABAA-mediated spontaneous postsynaptic potentials (PSPs), some GC exhibited spontaneous slow hyperpolarizations (SH). The SH were more commonly observed in a high concentration of external potassium. 2-Hydroxysaclofen, a GABAB antagonist, reduced the SH. Focal stimulation of the perforant path (PP) in the subiculum with a single pulse evoked a depolarization followed by a SH, which were both abolished by the excitatory amino acid (EAA) blockers, 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV). When evoked with a train of pulses, the SH was unaffected by the EAA blockers in 40% of the cells, suggesting either the existence of a GABAergic PP, or an unidentified polysynaptic mechanism. In control, the synaptic response to PP stimulation was superficially similar whether the stimulus was applied in the subiculum or stratum moleculare. However, in presence of bicuculline, the subicular PSP was followed by a train of PSPs occurring at a constant frequency of 25 Hz. This 'reverberating' effect of bicuculline was decreased in presence of APV and was abolished in slices in which the excitatory transmission had been interrupted downstream from CA3 neurons, suggesting that reverberation required the integrity of the hippocampo-entorhinal loop. By contrast, bicuculline decreased the amplitude of the stratum moleculare PSP. It is concluded that GC receive tonic inhibition from GABA acting at GABAA and GABAB receptors. The role of GABAB receptors is unclear; by contrast, GABAA-mediated inhibition prevents GC from reverberated excitation. The probability of occurrence of reverberation is higher during activation of the whole temporo-ammonic pathway and is partly dependent on the activation of N-methyl-D-aspartate (NMDA) receptors. Thus, the in vitro brain slice can be used as a model to study reverberation which has been recently demonstrated to underlie epileptiform discharges in the whole brain preparation.
Piguet
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Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011810:Quinoxalines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; C057491:2-hydroxysaclofen; D001640:Bicuculline