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J Physiol Volume 582, Number 3, 1163-1178, August 1, 2007 DOI: 10.1113/jphysiol.2007.134460
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NEUROSCIENCE

The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus

Joseph Glykys1 and Istvan Mody1

1 Interdepartmental PhD Program for Neuroscience and Departments of Neurology and Physiology, The David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA

The extracellular space of the brain contains {gamma}-aminobutyric acid (GABA) that activates extrasynaptic GABAA receptors mediating tonic inhibition. The source of this GABA is uncertain: it could be overspill of vesicular release, non-vesicular leakage, reverse transport, dying cells or glia. Using a novel approach, we simultaneously measured phasic and tonic inhibitory currents and assessed their correlation. Enhancing or diminishing vesicular GABA release in hippocampal neurons caused highly correlated changes in the two inhibitions. During high-frequency phasic inhibitory bursts, tonic current was also enhanced as shown by simulating the summation of IPSCs and by recordings in knockout mice devoid of tonic inhibitory current. When vesicular release was reduced by blocking action potentials or the vesicular GABA transporter, phasic and tonic currents decreased in a correlated fashion. Our results are consistent with most of hippocampal tonic inhibitory current being mediated by GABA released from the very vesicles responsible for activating phasic inhibition.

(Received 12 April 2007; accepted after revision 18 May 2007; first published online 24 May 2007)
Corresponding author I. Mody: UCLA School of Medicine, Department of Neurology, NRB1 Room 575D, 635 Charles E. Young Dr. South, Los Angeles, CA 90095, USA.  Email: mody{at}ucla.edu




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J. Glykys, E. O. Mann, and I. Mody
Which GABAA Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus?
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Differential Tonic GABA Conductances in Striatal Medium Spiny Neurons
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