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Acta Physiologica 2008; Volume 193, Supplement 664
Scandinavian Physiological Society’s Annual Meeting 2008
8/15/2008-8/17/2008
Oulu, Finland
GABA-A RECEPTORS MEDIATING TONIC INHIBITION IN THE NEOCORTEX
Abstract number: S0401
JENSEN1 K
1Synaptic Physiology Laboratory, Institute of Physiology and Biophysics 1160, University of Aarhus, Denmark
GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the mammalian central nervous system. GABA activates GABA-A receptors, which are pentameric chloride channels localized at synapses, and at locations away from the synaptic cleft so called extrasynaptic receptors. At synapses, GABA-A receptor activation leads to fast phasic signaling on the millisecond timescale shaped by the rapid GABA transient. Extrasynaptically, elevated extracellular GABA levels may activate receptors on a slower timescale leading to tonic inhibition. Prototypical extrasynaptic GABA-A receptors contain combinations of alpha4 and delta subunits, which confer a high affinity for GABA and little desensitization. We investigated tonic inhibition in mouse neocortex using whole-cell patch-clamp recordings in brain slices. In layer 2/3 pyramidal cells, elevated GABA levels led to significant a tonic current revealed by the GABA- A receptor antagonist SR95531. THDOC, a delta- subunit selective GABA-A modulator and neurosteroid, strongly enhanced the tonic current, while the delta-subunit selective agonist THIP also induced a clear tonic current. The benzodiazepine zolpidem had no effect on tonic GABA-A mediated currents. In layer 5 of the neocortex, which has a lower level of delta- subunit expression, pyramidal cells displayed a diminished tonic current. Finally, regular- spiking somatostatin-positive interneurons were completely devoid of tonic inhibition in response to GABA, THIP, or THDOC. In conclusion, delta-subunits contributes to the tonic inhibition in mouse neocortex in a cell- type specific manner. It is likely that tonic GABA-A receptor mediated inhibition and its enhancement by neurosteroids will only affect certain neurons in the cortical network.
To cite this abstract, please use the following information:
Acta Physiologica 2008; Volume 193, Supplement 664 :S0401