Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice In Vivo

Neuron. 2017 Jan 18;93(2):308-314. doi: 10.1016/j.neuron.2016.12.018. Epub 2016 Dec 29.

Abstract

Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo.

Keywords: CA1 region; EPSCs; GABAergic synapses; IPSCs; PV(+) interneurons; hippocampus; in vivo recording; in vivo voltage clamp; network oscillations; sharp wave-ripples.

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / physiology*
  • Electroencephalography Phase Synchronization
  • Excitatory Postsynaptic Potentials / physiology*
  • Hippocampus / physiology
  • Inhibitory Postsynaptic Potentials / physiology*
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Mice
  • Neural Inhibition
  • Optogenetics
  • Parvalbumins / metabolism
  • Wakefulness

Substances

  • Parvalbumins