Distinct Functional Groups Emerge from the Intrinsic Properties of Molecularly Identified Entorhinal Interneurons and Principal Cells

Cereb Cortex. 2017 Jun 1;27(6):3186-3207. doi: 10.1093/cercor/bhw143.


Inhibitory interneurons are an important source of synaptic inputs that may contribute to network mechanisms for coding of spatial location by entorhinal cortex (EC). The intrinsic properties of inhibitory interneurons in the EC of the mouse are mostly undescribed. Intrinsic properties were recorded from known cell types, such as, stellate and pyramidal cells and 6 classes of molecularly identified interneurons (regulator of calcineurin 2, somatostatin, serotonin receptor 3a, neuropeptide Y neurogliaform (NGF), neuropeptide Y non-NGF, and vasoactive intestinal protein) in acute brain slices. We report a broad physiological diversity between and within cell classes. We also found differences in the ability to produce postinhibitory rebound spikes and in the frequency and amplitude of incoming EPSPs. To understand the source of this intrinsic variability we applied hierarchical cluster analysis to functionally classify neurons. These analyses revealed physiologically derived cell types in EC that mostly corresponded to the lines identified by biomarkers with a few unexpected and important differences. Finally, we reduced the complex multidimensional space of intrinsic properties to the most salient five that predicted the cellular biomolecular identity with 81.4% accuracy. These results provide a framework for the classification of functional subtypes of cortical neurons by their intrinsic membrane properties.

Keywords: cell functional classification; entorhinal cortex; grid cells; interneurons; intrinsic properties.

MeSH terms

  • Animals
  • Biophysics
  • Cell Count
  • Cluster Analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Electric Stimulation
  • Entorhinal Cortex / cytology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • In Vitro Techniques
  • Interneurons / classification*
  • Interneurons / physiology*
  • Intracellular Signaling Peptides and Proteins
  • Membrane Potentials / physiology*
  • Mice
  • Mice, Transgenic
  • Neuropeptide Y / genetics
  • Neuropeptide Y / metabolism
  • Parvalbumins / genetics
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques
  • Proteins / genetics
  • Proteins / metabolism
  • Receptors, Serotonin, 5-HT3 / genetics
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vasoactive Intestinal Peptide / genetics
  • Vasoactive Intestinal Peptide / metabolism


  • DNA-Binding Proteins
  • Dscr1l1 protein, mouse
  • Grhl3 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptide Y
  • Parvalbumins
  • Proteins
  • Receptors, Serotonin, 5-HT3
  • Transcription Factors
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Vasoactive Intestinal Peptide