Serotonin 3A receptor subtype as an early and protracted marker of cortical interneuron subpopulations

Cereb Cortex. 2010 Oct;20(10):2333-47. doi: 10.1093/cercor/bhp310. Epub 2010 Jan 18.


To identify neocortical neurons expressing the type 3 serotonergic receptor, here we used transgenic mice expressing the enhanced green fluorescent protein (GFP) under the control of the 5-HT(3A) promoter (5-HT(3A):GFP mice). By means of whole-cell patch-clamp recordings, biocytin labeling, and single-cell reversed-transcriptase polymerase chain reaction on acute brain slices of 5-HT(3A):GFP mice, we identified 2 populations of 5-HT(3A)-expressing interneurons within the somatosensory cortex. The first population was characterized by the frequent expression of the vasoactive intestinal peptide and a typical bipolar/bitufted morphology, whereas the second population expressed predominantly the neuropeptide Y and exhibited more complex dendritic arborizations. Most interneurons of this second group appeared very similar to neurogliaform cells according to their electrophysiological, molecular, and morphological properties. The combination of 5-bromo-2-deoxyuridine injections with 5-HT(3A) mRNA detection showed that cortical 5-HT(3A) interneurons are generated around embryonic day 14.5. Although at this stage the 5-HT(3A) receptor subunit is expressed in both the caudal ganglionic eminence and the entopeduncular area, homochronic in utero grafts experiments revealed that cortical 5-HT(3A) interneurons are mainly generated in the caudal ganglionic eminence. This protracted expression of the 5-HT(3A) subunit allowed us to study specific cortical interneuron populations from their birth to their final functional phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bromodeoxyuridine / metabolism
  • COUP Transcription Factor II / metabolism
  • Cell Movement / physiology
  • Embryo, Mammalian
  • Female
  • Flow Cytometry / methods
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Green Fluorescent Proteins / genetics
  • Humans
  • In Vitro Techniques
  • Interneurons / classification*
  • Interneurons / metabolism*
  • Male
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Neuropeptide Y / metabolism
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques
  • Pregnancy
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Receptors, Serotonin, 5-HT3 / genetics
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Somatosensory Cortex / cytology*
  • Statistics, Nonparametric
  • Vasoactive Intestinal Peptide / metabolism


  • COUP Transcription Factor II
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Nr2f2 protein, mouse
  • Parvalbumins
  • Protein Subunits
  • Receptors, Serotonin, 5-HT3
  • Green Fluorescent Proteins
  • Vasoactive Intestinal Peptide
  • Bromodeoxyuridine