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Cell Type–Specific GABA_A Receptor–Mediated Tonic Inhibition in Mouse Neocortex

Synaptic Physiology Laboratory, Institute of Physiology and Biophysics, University of Aarhus, Aarhus, Denmark

Submitted 5 November 2007; accepted in final form 5 May 2008

Activity of extrasynaptic GABA_A receptors mediating tonic inhibition is thought to play an important role for the excitability of the mammalian cerebral cortex. However, little is known about the cell type–specific expression of tonic inhibition in particular types of cortical interneurons. Here, we used transgenic mice expressing green fluorescent protein (GFP) in somatostatin-positive (SOM) interneurons and investigated tonic inhibition in SOM interneurons versus pyramidal cells in neocortical layers 2/3. In brain slices, pyramidal cells showed a tonic current of 66 ± 19 pA in response to the -subunit selective GABA_A agonist THIP (1 µM). On the other hand, tonic inhibition was absent in SOM interneurons (8 ± 1 pA) in response to THIP. As opposed to pyramidal cells, SOM interneurons were also insensitive to the -subunit preferring neurosteroid allotetrahydrodeoxycorticosterone (THDOC) (100 nM) and to elevated endogenous GABA levels in the slice. Finally, SOM interneurons received only 45% of the phasic charge transfer during GABA_A receptor–mediated synaptic activity compared with pyramidal cells. Altogether, our study indicates that SOM interneurons receive relatively weak inhibitory input and cannot be brought under the influence of tonic inhibition.