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

Nature Neuroscience volume 13, pages 205–212 (2010)Cite this article

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Abstract

Gamma-frequency oscillations depend on phasic synaptic GABAA receptor (GABAAR)-mediated inhibition to synchronize spike timing. The spillover of synaptically released GABA can also activate extrasynaptic GABAARs, and such tonic inhibition may also contribute to modulating network dynamics. In many neuronal cell types, tonic inhibition is mediated by δ subunit–containing GABAARs. We found that the frequency of in vitro cholinergically induced gamma oscillations in the mouse hippocampal CA3 region was increased by the activation of NMDA receptors (NMDARs) on interneurons. The NMDAR-dependent increase of gamma oscillation frequency was counteracted by the tonic inhibition of the interneurons mediated by δ subunit–containing GABAARs. Recordings of synaptic currents during gamma activity revealed that NMDAR-mediated increases in oscillation frequency correlated 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.

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Figure 1: Cholinergic activation induces high-frequency γ oscillations in hippocampal slices from adult Gabrd−/− mice.
Figure 2: Hippocampal CA3 interneurons are disinhibited in adult Gabrd−/− mice.
Figure 3: Hippocampal CA3 interneurons in adult Gabrd−/− mice are more sensitive to NMDAR-mediated excitation.
Figure 4: Activation of NMDAR increases the frequency of cholinergically induced γ oscillations in juvenile slices.
Figure 5: High-frequency γ oscillations depend on AMPAR-mediated excitation.
Figure 6: The lag between synaptic inhibition and excitation disappears as the γ oscillation frequency increases.

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Change history

  • 27 December 2009

    In the version of this article initially published, the first name of the corresponding author was misspelled. The correct name is "Istvan Mody." This has been corrected in all versions of the article.

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Acknowledgements

This research was funded by a Epilepsy Foundation Postdoctoral Fellowship to E.O.M. and US National Institutes of Health grants NS30549 and NS02808 and the Coelho Endowment to I.M.

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  1. Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, California, USA

    Edward O Mann & Istvan Mody

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  1. Edward O Mann
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E.O.M. conducted the experiments and analysis. I.M. supervised the project. E.O.M. and I.M. wrote the manuscript.

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Correspondence to Istvan Mody.

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Mann, E., Mody, I. Control of hippocampal gamma oscillation frequency by tonic inhibition and excitation of interneurons. Nat Neurosci 13, 205–212 (2010). https://doi.org/10.1038/nn.2464

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