Satb1 Is an Activity-Modulated Transcription Factor Required for the Terminal Differentiation and Connectivity of Medial Ganglionic Eminence-Derived Cortical Interneurons

J Neurosci. 2012 Dec 5;32(49):17690-705. doi: 10.1523/JNEUROSCI.3583-12.2012.

Abstract

Although previous work identified transcription factors crucial for the specification and migration of parvalbumin (PV)-expressing and somatostatin (SST)-expressing interneurons, the intrinsic factors required for the terminal differentiation, connectivity, and survival of these cell types remain uncharacterized. Here we demonstrate that, within subpopulations of cortical interneurons, Satb1 (special AT-rich binding protein) promotes terminal differentiation, connectivity, and survival in interneurons that express PV and SST. We find that conditional removal of Satb1 in mouse interneurons results in the loss of a majority of SST-expressing cells across all cortical layers, as well as some PV-expressing cells in layers IV and VI, by postnatal day 21. SST-expressing cells initially migrate to the cortex in Satb1 mutant mice, but receive reduced levels of afferent input and begin to die during the first postnatal week. Electrophysiological characterization indicates that loss of Satb1 function in interneurons results in a loss of functional inhibition of excitatory principal cells. These data suggest that Satb1 is required for medial ganglionic eminence-derived interneuron differentiation, connectivity, and survival.

MeSH terms

  • Animals
  • Brain Waves / physiology
  • Cell Differentiation / physiology*
  • Cell Movement / physiology
  • Cell Survival / physiology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • Excitatory Postsynaptic Potentials / physiology
  • Gene Expression Regulation, Developmental / physiology
  • Interneurons / cytology
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Matrix Attachment Region Binding Proteins / metabolism
  • Matrix Attachment Region Binding Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / physiology
  • Parvalbumins / metabolism
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / physiology*
  • Somatostatin / metabolism
  • Transcription Factors / metabolism
  • Transcription Factors / physiology

Substances

  • Matrix Attachment Region Binding Proteins
  • Parvalbumins
  • Satb1 protein, mouse
  • Transcription Factors
  • Somatostatin