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The Journal of Neuroscience, February 6, 2008, 28(6):1421-1426; doi:10.1523/JNEUROSCI.4751-07.2008

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Brief Communications
Which GABA_A Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus?

Joseph Glykys,^1,2 Edward O. Mann,² and Istvan Mody^1,2

¹Interdepartmental PhD Program for Neuroscience and ²Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, California 90095

Correspondence should be addressed to Istvan Mody at the above address. Email: mody{at}ucla.edu

GABA_A receptors (GABA_ARs) assembled of different subunits mediate tonic and phasic inhibition in hippocampal neurons. CA1/CA3 pyramidal cells (PCs) predominantly express 5 subunits whereas dentate gyrus granule cells (DGGCs) and molecular layer (ML) interneurons predominantly express subunits. Both 5- and -containing GABA_ARs mediate tonic inhibition. We have shown previously that mice lacking 5 subunits (Gabra5^–/–) have a residual tonic current in CA1/CA3 PCs because of an upregulation of subunits, but the basis of the residual tonic current in DGGCs and ML interneurons of mice lacking the subunit (Gabrd^–/–) is still unknown. We now show that wild-type DGGCs have a small tonic current mediated by 5 subunit-containing GABA_ARs responsible for 29% of the total tonic current. To better identify the GABA_ARs mediating tonic inhibition in hippocampal neurons, we generated mice lacking both 5 and subunits (Gabra5/Gabrd^–/–). Recordings from CA1/CA3 PCs, DGGCs, and ML interneurons in these mice show an absence of tonic currents without compensatory changes in spontaneous IPSCs (sIPSCs), sEPSCs, and membrane resistance. The absence of tonic inhibition results in spontaneous gamma oscillations recordable in vitro in the CA3 pyramidal layer of these mice, which can be mimicked in wild-type mice by blocking 5 subunit-containing GABA_ARs with 50 nM L-655,708. In conclusion, depending on the cell type, the 5 and subunits are the principal GABA_AR subunits responsible for mediating the lion's share of tonic inhibition in hippocampal neurons.

Key words: tonic inhibition; 5; ; hippocampus; gamma oscillations; phasic inhibition

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Received Oct. 19, 2007; revised Nov. 21, 2007; accepted Dec. 12, 2007.

Correspondence should be addressed to Istvan Mody at the above address. Email: mody{at}ucla.edu

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