Structural development and dorsoventral maturation of the medial entorhinal cortex

Elife. 2016 Apr 2:5:e13343. doi: 10.7554/eLife.13343.


We investigated the structural development of superficial-layers of medial entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin - a marker of immature neurons - suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal entorhinal cortex, where small spatial-scales are represented. Maturation of ventral-entorhinal-microcircuits - representing larger spatial-scales - follows later around the onset of exploratory behavior.

Keywords: calbindin patches; doublecortin; immature neurons; medial entorhinal cortex; neuroscience; parasubiculum; pyramidal neurons; rat.

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Calbindins / analysis
  • Calmodulin-Binding Proteins / analysis
  • Cell Differentiation*
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Entorhinal Cortex / embryology*
  • Gene Expression
  • Membrane Proteins / analysis
  • Microtubule-Associated Proteins / analysis
  • Neurons / chemistry
  • Neurons / physiology*
  • Neuropeptides / analysis
  • Rats
  • Reelin Protein


  • Biomarkers
  • Calbindins
  • Calmodulin-Binding Proteins
  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Reelin Protein
  • Reln protein, rat
  • WFS1 protein, rat

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.