Activity Regulates Cell Death within Cortical Interneurons through a Calcineurin-Dependent Mechanism

Cell Rep. 2018 Feb 13;22(7):1695-1709. doi: 10.1016/j.celrep.2018.01.007.


We demonstrate that cortical interneurons derived from ventral eminences, including the caudal ganglionic eminence, undergo programmed cell death. Moreover, with the exception of VIP interneurons, this occurs in a manner that is activity-dependent. In addition, we demonstrate that, within interneurons, Calcineurin, a calcium-dependent protein phosphatase, plays a critical role in sequentially linking activity to maturation (E15-P5) and survival (P5-P20). Specifically, embryonic inactivation of Calcineurin results in a failure of interneurons to morphologically mature and prevents them from undergoing apoptosis. By contrast, early postnatal inactivation of Calcineurin increases apoptosis. We conclude that Calcineurin serves a dual role of promoting first the differentiation of interneurons and, subsequently, their survival.

Keywords: Calcineurin; cell death; cortical interneurons; development; maturation; neuronal activity.

Publication types

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

MeSH terms

  • Animals
  • Calcineurin / metabolism*
  • Calcium / metabolism
  • Cell Count
  • Cell Death
  • Cell Survival
  • Cerebral Cortex / cytology*
  • Embryo, Mammalian / cytology
  • Interneurons / cytology*
  • Interneurons / metabolism
  • Median Eminence / metabolism
  • Mice
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Signal Transduction
  • Solubility
  • Time Factors
  • bcl-2-Associated X Protein / metabolism


  • bcl-2-Associated X Protein
  • Calcineurin
  • Calcium