An electrophysiological model of GABA-mediated neurotransmission

Abstract Electrical stimulation of the perforant pathway in anesthetized rats resulted in excitation followed by inhibition of granule cells in the hippocampal dentate gyrus. Physiological, biochemical and immunocytochemical evidence suggests that inhibition of granule cell activity is mediated by recurrent collateral activation of an inhibitory GABA-containing interneuron. The effects on recurrent inhibition of agents which impair or facilitate GABAergic transmission were studied by recording single unit activity after microiontophoretic or systemic application of drugs. Administration of the GABA antagonist bicuculline reduced recurrent inhibition in the dentate gyrus. The GABA agonist, isonipecotic acid, prolonged the inhibition. l -2,4-Diaminobutyric acid and guvacine, in vitro inhibitors of GABA uptake, enhanced the duration of recurrent inhibition up to 75% when given iontophoretically. Strychnine had no effect on the duration of recurrent inhibition. Blockade of GABA synthesis with isoniazid markedly reduced or abolished the inhibition. These results indicate: (1) recurrent inhibition in the dentate gyrus is mediated by synaptically-released GABA; (2) uptake into neurons and/or glia limits the duration of action of synaptically-released GABA in vivo; (3) the recurrent inhibition system in the dentate gyrus is a useful model for evaluating drug effects on GABAergic neurotransmission.