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Self-Organizing Properties of Neocortical Circuits

English title Self-Organizing Properties of Neocortical Circuits
Applicant Jabaudon Denis
Number 157846
Funding scheme Temporary Backup Schemes
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2015 - 31.03.2020
Approved amount 2'108'800.00
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Keywords (2)

circuit assembly; neuronal diversity

Lay Summary (French)

Lead
Le cortex cérébral est composé d'une variété de neurones qui s'assemblent en des circuits au cours du développement. Il est important de comprendre les mécanismes qui contrôlent la formation de ces circuits car ils sont responsables de nos performances sensorielles, motrices, et cognitives, et sont atteints dans des maladies neurodégénératives, neuropsychiatriques, et dans les lésions cérébrales.
Lay summary

Dans ce contexte, ce projet de recherche vise à identifier les programmes génétiques qui contrôlent la génération de ces neurones, leur diférentiation, leur assemblage en circuits et leur capacité à s'organiser en réseau. Ces expériences permettront d'identifier les mécanismes intrinsèques et extrinsèques qui contrôlent la formation du cortex cérébral dans le but de développer des nouvelles stratégies thérapeutiques des maladies neurodégénératives, ou neurodéveloppementales.

Direct link to Lay Summary Last update: 15.02.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex
Telley L., Agirman G., Prados J., Amberg N., Fièvre S., Oberst P., Bartolini G., Vitali I., Cadilhac C., Hippenmeyer S., Nguyen L., Dayer A., Jabaudon D. (2019), Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex, in Science, 364(6440), eaav2522-eaav2522.
Progenitor Hyperpolarization Regulates the Sequential Generation of Neuronal Subtypes in the Developing Neocortex
Vitali Ilaria, Fièvre Sabine, Telley Ludovic, Oberst Polina, Bariselli Sebastiano, Frangeul Laura, Baumann Natalia, McMahon John J., Klingler Esther, Bocchi Riccardo, Kiss Jozsef Z., Bellone Camilla, Silver Debra L., Jabaudon Denis (2018), Progenitor Hyperpolarization Regulates the Sequential Generation of Neuronal Subtypes in the Developing Neocortex, in Cell, 174(5), 1264-1276.e15.
Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex
Telley L., Govindan S., Prados J., Stevant I., Nef S., Dermitzakis E., Dayer A., Jabaudon D. (2016), Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex, in Science, 351(6280), 1443-1446.

Associated projects

Number Title Start Funding scheme
146337 Molecular Identity and Development of Layer 4 Thalamorecipient Neurons of the Neocortex 01.08.2013 SNSF Professorships
160164 Building cortical sensorimotor circuits: Molecular controls over local and long-distance connectivity 01.08.2015 Project funding (Div. I-III)
164091 Identifying environmental controls over the transcriptional activity of single cells across organs and systems 01.12.2015 R'EQUIP
179423 Cellular and Genetic Mechanisms of Progenitor Fate Plasticity in the Neocortex 01.08.2018 Project funding (Div. I-III)

Abstract

The cerebral cortex is composed of distinct neuronal cell types, which assemble into specific intracortical circuits during development. Understanding the molecular and cellular mechanisms of this assembly is essential, because these circuits underlie most of our sensory, motor, and cognitive abilities, and are disrupted in neurodegenerative diseases, stroke, brain injury, and neurodevelopmental disorders. The current research program proposes to investigate the developmental genetic programs that control the generation of these neurons from progenitors (Work Package 1) and their early postmitotic specification (Work Package 2), their in vivo input-dependent assembly into circuits (Work Package 3), and finally, the self-organizing properties of the circuits they form (Work Package 4). Together, these experiments aim at characterizing the cell-intrinsic (i.e. genetic) and cell-extrinsic (i.e. input-dependent) processes controlling cortical circuit formation, with the long-term aim of providing new cell-based strategies for circuit repair.
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