GABA uptake regulates cortical excitability via cell type–specific tonic inhibition

Abstract
GABAA receptors can mediate both 'phasic' synaptic inhibition and a persistent 'tonic' form of signaling. We show that, in the presence of intact GABA uptake, guinea pig hippocampal interneurons, but not pyramidal cells, express a tonic GABAA receptor–mediated conductance. This conductance was pharmacologically distinct from spontaneous inhibitory postsynaptic currents (IPSCs). Inhibiting GABA uptake resulted in the expression of a comparable GABAA receptor–mediated tonic conductance in pyramidal cells. Reducing the tonic conductance in interneurons enhanced their excitability and the inhibitory drive to pyramidal cells. These results point to a role for cell type–dependent tonic inhibition in regulating cortical excitability.