Local generation of multineuronal spike sequences in the hippocampal CA1 region

Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10521-6. doi: 10.1073/pnas.1508785112. Epub 2015 Aug 3.


Sequential activity of multineuronal spiking can be observed during theta and high-frequency ripple oscillations in the hippocampal CA1 region and is linked to experience, but the mechanisms underlying such sequences are unknown. We compared multineuronal spiking during theta oscillations, spontaneous ripples, and focal optically induced high-frequency oscillations ("synthetic" ripples) in freely moving mice. Firing rates and rate modulations of individual neurons, and multineuronal sequences of pyramidal cell and interneuron spiking, were correlated during theta oscillations, spontaneous ripples, and synthetic ripples. Interneuron spiking was crucial for sequence consistency. These results suggest that participation of single neurons and their sequential order in population events are not strictly determined by extrinsic inputs but also influenced by local-circuit properties, including synapses between local neurons and single-neuron biophysics.

Keywords: hippocampus; mouse; optogenetics; ripples; temporal precision.

Publication types

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

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Brain / physiology
  • CA1 Region, Hippocampal / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology
  • Electrophysiology
  • Female
  • Interneurons / physiology
  • Light
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Neurological
  • Nerve Net / physiology
  • Neurons / physiology*
  • Optogenetics
  • Oscillometry
  • Probability
  • Promoter Regions, Genetic
  • Pyramidal Cells / cytology


  • Calcium-Calmodulin-Dependent Protein Kinase Type 2