title: GABAergic suppression prevents the appearance and subsequent fatigue of an NMDA receptor-mediated potential in neocortex.
abstract: We have investigated the regulation of an N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potential by gamma-aminobutyric acid (GABA)-mediated inhibition using extracellular and whole-cell voltage clamp recordings in rat auditory cortex in vitro. Single afferent stimulus pulses at low intensity elicited a slow extracellular negativity (Component C) that was mediated by NMDA receptors. At higher intensities, Component C was suppressed by recruitment of GABAergic inhibition. To understand the actions of GABAergic inhibition on Component C, we determined the effects of: (i) paired-pulse stimulation, which depresses GABAergic inhibition; (ii) pharmacological antagonism of GABA receptors; and (iii) afferent stimulation in slices from neonatal rats prior to the development of cortical inhibition. The results indicate that GABAergic inhibition prevents Component C from occurring, thereby preventing its reduction upon repeated stimulation. Whole-cell voltage clamp recordings were used to test the hypothesis that GABAergic suppression occurred by way of membrane hyperpolarization. At hyperpolarized holding potentials no NMDA receptor-mediated synaptic current was elicited, even with paired-pulse stimulation. At depolarized holding potentials a significant NMDA synaptic current was elicited despite the presence of GABAergic synaptic currents. We conclude that membrane hyperpolarization by GABAergic inhibition prevents the appearance and subsequent fatigue of an NMDA receptor-mediated synaptic potential. Reduction of inhibition can act as a 'switch' to fully release the NMDA potential as frequently as once every 10-20 s.
authors.affiliation: Department of Neuroscience, University of California, Riverside 92521, USA.
authors.forename: R
authors.initials: R
authors.lastname: Metherate
authors.forename: J H
authors.initials: JH
authors.lastname: Ashe
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010421:Pentanoic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D010421:Pentanoic Acids; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; C038780:n-pentanoic acid