GABAA receptor-mediated mechanisms contribute to frequency-dependent depression of IPSPs in the hippocampus.
Intracellular recordings from in vitro guinea-pig hippocampal slices were obtained to investigate the mechanisms underlying activity-dependent depression of inhibitory postsynaptic potentials (IPSPs) in CA1 pyramidal neurons. IPSPs were studied following blockade of glutamatergic transmission. Attenuation of both fast and slow IPSP components was apparent at stimulus rates of > 0.2 Hz, but the late IPSP showed depression at even lower rates of stimulation. Overlap of these events made resolving response components during depression difficult. Fast IPSPs were isolated using CsCl-filled microelectrodes, blocking slow potassium-dependent IPSPs and reversing the chloride gradient. Under this condition repetitive stimulation did not induce IPSP depression. Other experiments showed slow IPSP depression at stimulus rates of < 0.5 Hz was relieved in the presence of picrotoxin which antagonizes GABAA events. These results suggest that activity-dependent depression of the fast IPSP results largely from chloride accumulation as a consequence of repetitive activation. Depression of the slow IPSP appears to arise from at least two components: (1) a masking of the slow hyperpolarization resulting from an apparent increase in the depolarizing GABA response due to chloride accumulation; and (2) a novel process involving GABAA receptors, perhaps mediated through presynaptic inhibition.
Department of Neurology, State University of New York, Health Science Center, Brooklyn 11203.
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Benardo
D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D008839:Microelectrodes; D011712:Pyramidal Tracts / Q000166:cytology / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000596:Amino Acids; D002712:Chlorides; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid