Control of hippocampal gamma oscillation frequency by tonic inhibition and excitation of interneurons

Gamma-frequency oscillations depend on phasic synaptic GABA(A) receptor-mediated inhibition to synchronize spike timing. The spillover of synaptically-released GABA can also activate extrasynaptic GABA(A) receptors, and such tonic inhibition may also contribute to modulating network dynamics. In many neuronal cell types, tonic inhibition is mediated by δ subunit-containing GABA(A) receptors. We show that the frequency of in vitro cholinergically-induced gamma oscillations in the mouse hippocampal CA3 region is increased by the activation of NMDA receptors (NMDAR) on interneurons. The NMDAR-dependent increase of gamma oscillation frequency is counteracted by the tonic inhibition of the interneurons mediated by δ subunit-containing GABA(A) receptors. Recordings of synaptic currents during gamma activity show that NMDAR-mediated increases in oscillation frequency correlate with a progressive synchronization of phasic excitation and inhibition in the network. Thus, the balance between tonic excitation and tonic inhibition of interneurons may modulate gamma frequency by shaping interneuronal synchronization.