Developmental mechanisms of brain disorders

Leader

Co-Leaders

Research center

17 rue du Fer à Moulin
75005 Paris

Institution

Inserm
Université Pierre et Marie Curie
Labex BIOPSY
ED158
Université Pierre et Marie Curie

Laboratory

Phone: 33(0) 1 45 87 61 28
Fax: 33(0)145 87 61 35
UMRS 839

Mots clefs

migration
Cortex
Retina
serotonin
axon guidance
Neural activity
Critical periods
 

publications

Fernandez SP, Muzerelle A, Scotto-Lomassese S, Barik J, Gruart A, Delgado-García JM, Gaspar P. Constitutive and Acquired Serotonin Deficiency Alters Memory and Hippocampal Synaptic Plasticity. Neuron. 2016 Oct 19;92(2):435-448. doi: 10.1016/j.neuron.2016.09.020. 

Muzerelle A, Scotto-Lomassese S, Bernard JF, Soiza-Reilly M, Gaspar P. (2014) Conditional anterograde tracing reveals distinct targeting of individual serotonin cell groups (B5-B9) to the forebrain and brainstem. Brain Struct Funct  Nov 18  PubMed PMID: 25403254 

 Assali A, Gaspar P, Rebsam A. Activity dependent mechanisms of visual map formation--from retinal waves to molecular regulators. Semin Cell Dev Biol. 2014 Nov;35:136-46 

Luccardini C, Hennekinne L, Viou L, Yanagida M, Murakami F, Kessaris N, Ma X,  Adelstein RS, Mège RM, Métin C. ( 2013) N-cadherin sustains motility and polarity of future cortical interneurons during tangential migration. J Neurosci. 2013 Nov 13;33(46):18149-60.

Diaz S.L*, Narboux-Nême N*, Trowbridge S,  Scotto, S, Borgemann FK, Jessberger S, Giros B , Maroteaux L, Deneris E, Gaspar P (2013) Paradoxical increased survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin. Eur J Neuroscience. 38:2650-8.

Baudoin_ JP*, Viou* L, Launay P-S, Luccardini C, Espeso S, Kiyasova V, Irinopoulou T , Alvarez C,  Rio J-P, Boudier T, Lechaire J-P, Kessaris N,  Spassky N, Métin C. (2012) Tangentially migrating neurons assemble a primary cilium that promotes their re-orientation to the cortical plate. Neuron , 20;76 :1108-22. (* equal contribution).

Narboux-Nême N, Evrard A, Ferezou I, Erzurumlu RS, Kaeser PS, Lainé J, RossierJ, Ropert N, Südhof TC, Gaspar P. (2012) Neurotransmitter release at the thalamocortical synapse instructs barrel formation but not axon patterning in the somatosensory cortex. J Neurosci., 32:6183-6196.

Rebsam A, Bhansali P, Mason CA (2012) Eye-specific projections of retinogeniculate axons are altered in albino mice. J Neurosci  32(14): 4821-6

Narboux-Nême N, Angenard G, Mosienko V, Klempin F, Pitychoutis PM, Deneris E, Bader M, Giros B, Alenina N, Gaspar P. (2013) Postnatal growth defects in mice with constitutive depletion of central serotonin. ACS Chem Neurosci. ;4:171-81

Fields of research

Neurogenetics / neurodevelopment

Research Theme

Des évidences croissantes montrent l'implication d'anomalies développementales à l'origine de pathologies neuropsychiatriques. En effet des circuits neuronaux sous-tendent tous nos comportements du plus simple au plus complexe. La construction de ces réseaux débute pendant la vie embryonnaire, par la migration des neurones de leur lieu de naissance à leur emplacement définitif, et par la croissance des prologements axonaux qui se dirigent vers une cible précise grâce à des molécules de guidage. Le raffinement des connexions nerveuses implique par la suite l'activité synaptique et la consolidation ou non des réseaux formés.

Une programmation génétique orchestre la formation des circuits neuronaux, mais en interaction constante avec l'environnement, permettant une adaptation et un ajustement des circuits. Notre équipe étudie ces mécanismes dans le contexte de 3 systèmes modèles , les interneurones du cortex, le système sérotoninergique et le système visuel. Auxquels répondent des pathologies développementales telles que le retard mental, les pathologies anxio-dépressives, et des anomalies du développement du système visuel.

Nos programmes de recherche en cours concernent:


1) Rôle de Sonic hedgehog dans la migration des interneurones corticaux

2) Guidage moléculaire dans la formation des cartes visuelles, interaction avec l'activité neuronale spontanée.

3) Rôle de la sérotonine dans le développement des circuits reliant le cortex préfrontal et le raphe



Etudiants ENP

Jimmy OLUSAKIN

Membres de l'équipe

Sophie SCOTTO
Aude MUZERELLE
Mariano SOIZA-REILLY
Anne TEISSIER
Cédric FRANCIUS
Teng TENG
Claire LECLECH
Maria PEDRAZA
Delphine PRIEUR
Alexandra REBSAM

Lab rotation

Developmental defects of the visual system in albinism

Chercheur responsable: 

GASPAR Patricia

Dates: 

18 September 2017 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Sept-Dec 2017

~ Jan-March 2018

~ April-June 2018

Project

Brain function relies on the precise organization of neuronal connections during development. Alterations of any of these steps will have structural and functional consequences. We use the visual system to precisely study the mechanisms that regulate some of these developmental events and this project focuses on a rare disease, albinism, showing clear functional consequences arising from a developmental alteration. In albinism, a defect in melanin production leads to hypopigmentation, a hallmark of this disease, but also to important visual deficits due to abnormal development of the retina. This project aims to characterize the links between melanin production and retinal specification during development and their consequences on neuronal connections and activity within the retina. Furthermore, we will decipher how the albino mutation at the level of the retinal pigmented epithelium impact retinal development. For that, we will use a combination of in vivo approaches in mouse models and in vitro approaches. The student will use immunohistochemistry, fluorescence and confocal microscopy, calcium imaging and videomicroscopy as well as cell culture techniques. This study will shed lights on the pathophysiology of albinism and unravel mechanisms governing normal retinal development and visual neural circuit formation.

Contact

Institut du Fer à Moulin - 17 rue du fer à moulin 75005 Paris - +33 1 45 87 61 27 - alexandra.rebsam@inserm.fr


Superviseur: 

REBSAM Alexandra

Analysis of the migration of embryonic neurons in micropatterned environments

Chercheur responsable: 

METIN Christine

Dates: 

18 September 2017 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Sept-Dec 2017

~ Jan-March 2018

~ April-June 2018

Project

Our laboratory recently showed that the topography of the micro-environment influences the migratory properties of immature cortical interneurons. Interneurons migrating among round or square plots strongly differ in morphology and dynamics.  The stage will aim at characterizing the organization of the cytoskeleton (microtubules, acto-myosin) in interneurons migrating on each type of substrate using superresolution microscopy and live cell imaging. 

Contact

Institut du Fer à Moulin - 17, rue du fer à moulin 75005 Paris - +33 1 45 87 61 26 - Christine.metin@inserm.fr

Superviseur: 

METIN Christine