Grid-layout and theta-modulation of layer 2 pyramidal neurons in medial entorhinal cortex

Science. 2014 Feb 21;343(6173):891-6. doi: 10.1126/science.1243028. Epub 2014 Jan 23.


Little is known about how microcircuits are organized in layer 2 of the medial entorhinal cortex. We visualized principal cell microcircuits and determined cellular theta-rhythmicity in freely moving rats. Non-dentate-projecting, calbindin-positive pyramidal cells bundled dendrites together and formed patches arranged in a hexagonal grid aligned to layer 1 axons, parasubiculum, and cholinergic inputs. Calbindin-negative, dentate-gyrus-projecting stellate cells were distributed across layer 2 but avoided centers of calbindin-positive patches. Cholinergic drive sustained theta-rhythmicity, which was twofold stronger in pyramidal than in stellate neurons. Theta-rhythmicity was cell-type-specific but not distributed as expected from cell-intrinsic properties. Layer 2 divides into a weakly theta-locked stellate cell lattice and spatiotemporally highly organized pyramidal grid. It needs to be assessed how these two distinct principal cell networks contribute to grid cell activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Calbindins / analysis
  • Calbindins / metabolism
  • Dendrites / physiology
  • Dentate Gyrus / physiology
  • Entorhinal Cortex / cytology*
  • Entorhinal Cortex / metabolism
  • Entorhinal Cortex / physiology
  • Female
  • Male
  • Nerve Net*
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology*
  • Pyramidal Cells / ultrastructure*
  • Rats
  • Rats, Wistar
  • Staining and Labeling
  • Theta Rhythm*


  • Calbindins
  • Acetylcholine