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

Nat Neurosci. 2010 Feb;13(2):205-12. doi: 10.1038/nn.2464. Epub 2009 Dec 20.


Gamma-frequency oscillations depend on phasic synaptic GABA(A) receptor (GABA(A)R)-mediated inhibition to synchronize spike timing. The spillover of synaptically released GABA can also activate extrasynaptic GABA(A)Rs, and such tonic inhibition may also contribute to modulating network dynamics. In many neuronal cell types, tonic inhibition is mediated by delta subunit-containing GABA(A)Rs. 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 delta subunit-containing GABA(A)Rs. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • CA3 Region, Hippocampal / physiology*
  • Excitatory Postsynaptic Potentials
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials
  • Interneurons / physiology*
  • Male
  • Membrane Potentials
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Inhibition / physiology*
  • Periodicity
  • Receptors, AMPA / metabolism
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Time Factors


  • Receptors, AMPA
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate