Activity-dependent death of transient Cajal-Retzius neurons is required for functional cortical wiring
Martina Riva,
Ioana Genescu,
Chloé Habermacher,
David Orduz,
Fanny Ledonne,
Filippo M Rijli,
Guillermina López-Bendito,
Eva Coppola,
Sonia Garel,
Maria Cecilia Angulo,
Alessandra Pierani
Affiliations
Martina Riva
Institut Imagine, Université de Paris, Paris, France; Institut Jacques Monod, CNRS UMR 7592, Université de Paris, Paris, France; Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université de Paris, Paris, France
Ioana Genescu
Institut de Biologie de l’École Normale Supérieure (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France
Chloé Habermacher
Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université de Paris, Paris, France; INSERM U1128, Paris, France
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Guillermina López-Bendito
Instituto de Neurosciencias de Alicante, Universidad Miguel Hernandez, Sant Joan d’Alacant, Spain
Eva Coppola
Institut Imagine, Université de Paris, Paris, France; Institut Jacques Monod, CNRS UMR 7592, Université de Paris, Paris, France; Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université de Paris, Paris, France
Institut de Biologie de l’École Normale Supérieure (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France
Institut Imagine, Université de Paris, Paris, France; Institut Jacques Monod, CNRS UMR 7592, Université de Paris, Paris, France; Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université de Paris, Paris, France
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.
