Neuronal activity is required for the development of specific cortical interneuron subtypes

Nature. 2011 Apr 21;472(7343):351-5. doi: 10.1038/nature09865. Epub 2011 Apr 3.

Abstract

Electrical activity has been shown to regulate development in a variety of species and in various structures, including the retina, spinal cord and cortex. Within the mammalian cortex specifically, the development of dendrites and commissural axons in pyramidal cells is activity-dependent. However, little is known about the developmental role of activity in the other major cortical population of neurons, the GABA-producing interneurons. These neurons are morphologically and functionally heterogeneous and efforts over the past decade have focused on determining the mechanisms that contribute to this diversity. It was recently discovered that 30% of all cortical interneurons arise from a relatively novel source within the ventral telencephalon, the caudal ganglionic eminence (CGE). Owing to their late birth date, these interneurons populate the cortex only after the majority of other interneurons and pyramidal cells are already in place and have started to functionally integrate. Here we demonstrate in mice that for CGE-derived reelin (Re)-positive and calretinin (Cr)-positive (but not vasoactive intestinal peptide (VIP)-positive) interneurons, activity is essential before postnatal day 3 for correct migration, and that after postnatal day 3, glutamate-mediated activity controls the development of their axons and dendrites. Furthermore, we show that the engulfment and cell motility 1 gene (Elmo1), a target of the transcription factor distal-less homeobox 1 (Dlx1), is selectively expressed in Re(+) and Cr(+) interneurons and is both necessary and sufficient for activity-dependent interneuron migration. Our findings reveal a selective requirement for activity in shaping the cortical integration of specific neuronal subtypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Calbindin 2
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Movement* / drug effects
  • Cell Shape / drug effects
  • Cerebral Cortex / cytology*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Interneurons / cytology*
  • Interneurons / drug effects
  • Interneurons / metabolism*
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Pregnancy
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism
  • Receptors, Ionotropic Glutamate / antagonists & inhibitors
  • Receptors, Ionotropic Glutamate / metabolism
  • Reelin Protein
  • S100 Calcium Binding Protein G / metabolism
  • Serine Endopeptidases / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vasoactive Intestinal Peptide / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Calb2 protein, mouse
  • Calbindin 2
  • Cell Adhesion Molecules, Neuronal
  • Distal-less homeobox proteins
  • ELMO1 protein, mouse
  • Extracellular Matrix Proteins
  • Homeodomain Proteins
  • Kir2.1 channel
  • Nerve Tissue Proteins
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Ionotropic Glutamate
  • Reelin Protein
  • S100 Calcium Binding Protein G
  • Transcription Factors
  • Vasoactive Intestinal Peptide
  • Reln protein, mouse
  • Serine Endopeptidases