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 α5 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 α5−/− mice we investigated the role of α5 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 α5−/− than in WT slices. However, the change in frequency of gamma oscillations with increasing network drive seen in WT slices was absent in α5−/− 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 α5−/− 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.

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