5-HT(3A) receptor-bearing white matter interstitial GABAergic interneurons are functionally integrated into cortical and subcortical networks

J Neurosci. 2011 Nov 16;31(46):16844-54. doi: 10.1523/JNEUROSCI.0310-11.2011.


In addition to axons and surrounding glial cells, the corpus callosum also contains interstitial neurons that constitute a heterogeneous cell population. There is growing anatomical evidence that white matter interstitial cells (WMICs) comprise GABAergic interneurons, but so far there is little functional evidence regarding their connectivity. The scarcity of these cells has hampered electrophysiological studies. We overcame this hindrance by taking recourse to transgenic mice in which distinct WMICs expressed enhanced green fluorescence protein (EGFP). The neuronal phenotype of the EGFP-labeled WMICs was confirmed by their NeuN positivity. The GABAergic phenotype could be established based on vasoactive intestinal peptide and calretinin expression and was further supported by a firing pattern typical for interneurons. Axons and dendrites of many EGFP-labeled WMICs extended to the cortex, hippocampus, and striatum. Patch-clamp recordings in acute slices showed that they receive excitatory and inhibitory input from cortical and subcortical structures. Moreover, paired recordings revealed that EGFP-labeled WMICs inhibit principal cells of the adjacent cortex, thus providing unequivocal functional evidence for their GABAergic phenotype and demonstrating that they are functionally integrated into neuronal networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Axons / drug effects
  • Axons / physiology*
  • Carbachol / pharmacology
  • Cerebral Cortex / cytology*
  • Cholinergic Agonists / pharmacology
  • Corpus Callosum / cytology*
  • Corpus Callosum / metabolism
  • Dihydro-beta-Erythroidine / pharmacology
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Interneurons / cytology*
  • Interneurons / physiology
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Mice
  • Mice, Transgenic
  • Nerve Net / physiology
  • Nerve Tissue Proteins / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / genetics
  • Neurites / physiology
  • Neuroglia / metabolism
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques
  • Receptors, Serotonin, 5-HT3 / genetics
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Statistics, Nonparametric
  • Synaptic Potentials / drug effects
  • Synaptic Potentials / genetics
  • Vasoactive Intestinal Peptide / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • Cholinergic Agonists
  • Nerve Tissue Proteins
  • Parvalbumins
  • Receptors, Serotonin, 5-HT3
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Dihydro-beta-Erythroidine
  • Vasoactive Intestinal Peptide
  • gamma-Aminobutyric Acid
  • Carbachol
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • biocytin
  • Lysine