Parvalbumin interneurons provide grid cell-driven recurrent inhibition in the medial entorhinal cortex

Nat Neurosci. 2014 May;17(5):710-8. doi: 10.1038/nn.3696. Epub 2014 Apr 6.


Grid cells in the medial entorhinal cortex (MEC) generate metric spatial representations. Recent attractor-network models suggest an essential role for GABAergic interneurons in the emergence of the grid-cell firing pattern through recurrent inhibition dependent on grid-cell phase. To test this hypothesis, we studied identified parvalbumin-expressing (PV(+)) interneurons that are the most likely candidate for providing this recurrent inhibition onto grid cells. Using optogenetics and tetrode recordings in mice, we found that PV(+) interneurons exhibited high firing rates, low spatial sparsity and no spatial periodicity. PV(+) interneurons inhibited all functionally defined cell types in the MEC and were in turn recruited preferentially by grid cells. To our surprise, we found that individual PV(+) interneurons received input from grid cells with various phases, which most likely accounts for the broadly tuned spatial firing activity of PV(+) interneurons. Our data argue against the notion that PV(+) interneurons provide phase-dependent recurrent inhibition and challenge recent attractor-network models of grid cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Channelrhodopsins
  • Dependovirus / genetics
  • Entorhinal Cortex / cytology*
  • Humans
  • Interneurons / classification
  • Interneurons / physiology*
  • Lasers
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Maze Learning / physiology
  • Mice
  • Microinjections
  • Models, Neurological
  • Nerve Net / physiology*
  • Neural Inhibition / physiology*
  • Parvalbumins / metabolism*
  • Red Fluorescent Protein
  • Statistics, Nonparametric
  • Theta Rhythm / physiology
  • Transduction, Genetic


  • Channelrhodopsins
  • Luminescent Proteins
  • Parvalbumins