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This Article Full Text Full Text (PDF) All Versions of this Article: 559/3/721    most recent jphysiol.2004.071191v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Towers, S. K. Articles by Whittington, M. A. Search for Related Content PubMed PubMed Citation Articles by Towers, S. K. Articles by Whittington, M. A.

¹ School of Biomedical Sciences, University of Leeds, Leeds, LS2 9NQ, UK
² Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, CM20 2QR, UK
³ Department of Physiology and Pharmacology, State University of New York Health Science Center, Brooklyn, New York 11203, USA

Though all in vitro models of gamma frequency network oscillations are critically dependent on GABA_A receptor-mediated synaptic transmission little is known about the specific role played by different subtypes of GABA_A receptor. Strong expression of the 5 subunit of the GABA_A receptor is restricted to few brain regions, amongst them the hippocampal dendritic layers. Receptors containing this subunit may be expressed on the extrasynaptic membrane of principal cells and can mediate a tonic GABA_A conductance. Using hippocampal slices of wild-type (WT) and 5–/– mice we investigated the role of 5 subunits in the generation of kainate-induced gamma frequency oscillations (20–80 Hz). The change in power of the oscillations evoked in CA3 by increasing network drive (kainate, 50–400 nM) was significantly greater in 5–/– than in WT slices. However, the change in frequency of gamma oscillations with increasing network drive seen in WT slices was absent in 5–/– slices. Raising the concentration of extracellular GABA by bathing slices in the GABA transaminase inhibitor vigabatrin and blocking uptake with tiagabine reduced the power of gamma oscillations more in WT slices than 5–/– slices (43%versus 15%). The data suggest that loss of this GABA_A receptor subunit alters the dynamic profile of gamma oscillations to changes in network drive, possibly via actions of GABA at extrasynaptic receptors.

(Received 2 July 2004; accepted after revision 23 July 2004; first published online 29 July 2004)
Corresponding author M. A. Whittington: School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, UK. Email: m.a.whittington{at}leeds.ac.uk

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