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

Rashi Priya, Mercedes Francisca Paredes, Theofanis Karayannis, Nusrath Yusuf, Xingchen Liu, Xavier Jaglin, Isabella Graef, Arturo Alvarez-Buylla, Gord Fishell

Research output: Contribution to journalArticlepeer-review

Abstract

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. Priya et al. demonstrate that maturation and cell death within most populations of cortical interneurons is mediated by activity, which is transduced into intracellular signals through activation of the protein phosphatase Calcineurin. Thus, a single mechanism sequentially promotes interneuron differentiation and cell death in all interneurons except VIP-expressing cells.

Original languageEnglish (US)
Pages (from-to)1695-1709
Number of pages15
JournalCell Reports
Volume22
Issue number7
DOIs
StatePublished - Feb 13 2018

Keywords

  • Calcineurin
  • cell death
  • cortical interneurons
  • development
  • maturation
  • neuronal activity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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