Alpha 5 subunit-containing GABAA receptors affect the dynamic range of mouse hippocampal kainate-induced gamma frequency oscillations in vitro.

Though all in vitro models of gamma frequency network oscillations are critically dependent on GABAA receptor-mediated synaptic transmission little is known about the specific role played by different subtypes of GABAA receptor. Strong expression of the alpha5 subunit of the GABAA 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 GABAA conductance. Using hippocampal slices of wild-type (WT) and alpha5-/- mice we investigated the role of alpha5 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 alpha5-/- than in WT slices. However, the change in frequency of gamma oscillations with increasing network drive seen in WT slices was absent in alpha5-/- 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 alpha5-/- slices (43%versus 15%). The data suggest that loss of this GABAA receptor subunit alters the dynamic profile of gamma oscillations to changes in network drive, possibly via actions of GABA at extrasynaptic receptors.

Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice.

Neural processing occurs in parallel in distant cortical areas even for simple perceptual tasks. Associated cognitive binding is believed to occur through the interareal synchronization of rhythmic activity in the gamma (30-80 Hz) range. Such oscillations arise as an emergent property of the neuronal network and require conventional chemical neurotransmission. To test the potential role of gap junction-mediated electrical signaling in this network property, we generated mice lacking connexin 36, the major neuronal connexin. Here we show that the loss of this protein disrupts gamma frequency network oscillations in vitro but leaves high frequency (150 Hz) rhythms, which may involve gap junctions between principal cells (Schmitz et al., 2001), unaffected. Thus, specific connexins differentially deployed throughout cortical networks are likely to regulate different functional aspects of neuronal information processing in the mature brain.