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

Publication date: 13 February 2018
Source:Cell Reports, Volume 22, Issue 7
Author(s): Rashi Priya, Mercedes Francisca Paredes, Theofanis Karayannis, Nusrath Yusuf, Xingchen Liu, Xavier Jaglin, Isabella Graef, Arturo Alvarez-Buylla, Gord Fishell
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.

Graphical abstract

Teaser

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.


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