Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex

Cell Rep. 2018 Feb 13;22(7):1710-1721. doi: 10.1016/j.celrep.2018.01.064.


Cortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs) is established in the mammalian forebrain. CIs are generated in excess from basal forebrain progenitors, and their final numbers are adjusted via an intrinsically determined program of apoptosis that takes place during an early postnatal window. Here, we provide evidence that the extent of CI apoptosis during this critical period is plastic and cell-type specific and can be reduced in a cell-autonomous manner by acute increases in neuronal activity. We propose that the physiological state of the emerging neural network controls the activity levels of local CIs to modulate their numbers in a homeostatic manner.

Keywords: DREADS; Lhx6; activity-dependent plasticity; cortical interneurons; homeostatic plasticity; interneuron cell death; interneuron development; interneuron transplantations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Count
  • Cell Lineage
  • Cell Survival
  • Cellular Microenvironment
  • Cerebral Cortex / cytology*
  • Interneurons / cytology*
  • LIM-Homeodomain Proteins / deficiency
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Median Eminence / cytology
  • Mice, Transgenic
  • Mutation / genetics
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Inhibition*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome / genetics
  • Up-Regulation / genetics


  • LHX6 protein, mouse
  • LIM-Homeodomain Proteins
  • Nerve Tissue Proteins
  • Transcription Factors