Activity-dependent death of transient Cajal-Retzius neurons is required for functional cortical wiring.

Martina Riva,Filippo M Rijli,Guillermina López-Bendito,Eva Coppola,Fanny Ledonne,Sonia Garel,Chloé Habermacher,Alessandra Pierani,David Orduz,Maria Cecilia Angulo,Ioana Genescu

doi:10.7554/elife.50503

Abstract

Programmed cell death and early activity contribute to the emergence of functional cortical circuits. While most neuronal populations are scaled-down by death, some subpopulations are entirely eliminated, raising the question of the importance of such demise for cortical wiring. Here, we addressed this issue by focusing on Cajal-Retzius neurons (CRs), key players in cortical development that are eliminated in postnatal mice in part via Bax-dependent apoptosis. Using Bax-conditional mutants and CR hyperpolarization, we show that the survival of electrically active subsets of CRs triggers an increase in both dendrite complexity and spine density of upper layer pyramidal neurons, leading to an excitation/inhibition imbalance. The survival of these CRs is induced by hyperpolarization, highlighting an interplay between early activity and neuronal elimination. Taken together, our study reveals a novel activity-dependent programmed cell death process required for the removal of transient immature neurons and the proper wiring of functional cortical circuits.

Highlights

An emerging player in the assembly of neuronal networks is programmed cell death (PCD)
To decipher whether activity might regulate the death of specific subsets of Cajal-Retzius neurons (CRs) in vivo, we first overexpressed the hyperpolarizing channel Kir2.1 (R26Kir2.1mcherry/+) (Moreno-Juan et al, 2017) using the Np73cre/+ line
We found that the density of CRs in the somatosensory barrel cortex was unchanged in these animals at postnatal day 7 (P7), that is before CRs undergo massive cell death (Figure 1A and B)

Summary

Introduction

An emerging player in the assembly of neuronal networks is programmed cell death (PCD). Cajal-Retzius cells (CRs), the first-born cortical neurons lying in the superficial Layer I (LI), undergo extensive cell death in the mouse during the second postnatal week (Ledonne et al, 2016). CR play pivotal roles at multiple steps of early cortical development, in addition to their bestknown role in the control of radial migration (Ishii et al, 2016). They comprise three molecularly distinct subtypes which migrate from different sources that surround the cortical primordium: (i) septum

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