Research interests

Our team investigates Malformations of Cortical Development (MCDs) which are important causes of mental retardation and account for 20-40% of drug-resistant childhood epilepsy.
We conduct integrated multidisciplinary studies involving morphologists, molecular biologists and electrophysiologists. In addition, we have established collaborations with clinicians and geneticists (European EPICURE project) providing us with a transversal appreciation of our researches.
We concentrate our efforts on:

[1] the identification of new genes and molecular actors involved in normal migration processes and being altered on MCDs;

[2] a better understanding of the link between genotype and phenotype, and of the process leading to an abnormal migration pattern;

[3] the characterization of the physiopathological mechanisms responsible for epileptogenesis in MCDs, in order to precisely identify the seizure-generating zone, to describe its properties and the mechanisms of seizure generation, and to ultimately suggest new therapeutic approaches.

Specific projects

Our specific projects are the following:

  • aIdentification of new candidate genes for neuronal migration and MCDs
  • bMecanisms of genesis of MCDs
  • cMorphofunctional analysis of heterotopic networks
  • dFunctional repercussions of cortical migration disorders: analysis of DCX knockdown rats
a

Identification of new candidate genes for neuronal migration and MCDs

C Cardoso (PI)
with E Pallesi, A Carabalona, PPGI
This sub-project aims to identify new MCDs genes using an experimental approach enabling rapid functional evaluation of candidate genes potentially impacting neuronal migration.

b

Mecanisms of genesis of MCDs

C Cardoso (PI)
with A Carabalona, S Beguin, H Becq, E Pallesi, PPGI
This sub-project aims at understanding the pathophysiological basis of MCDs by taking advantage of our MCDs knockdown animal models developped by in utero RNAi.

c
Cluster of biocytin-filled ectopic cortical neurons (red/white) located within subcortical band heterotopia in a DCX knockdown rat (from Ackman et al. J Neurosci 2009)

Morphofunctional analysis of heterotopic networks

J-B Manent (PI)
with C Cardoso, L Petit, H Becq, I Jorquera, A Carabalona, PPGI
and collaborations with I Bureau, V Crepel and L Aniksztejn teams
In this sub-project, our aim is to provide a better description of heterotopic networks by combining multi-disciplinary circuit mapping methods: conventional neuroanatomical methods, molecular biological tools and laser scanning photostimulation.

d
Acute neocortical slice containing RFP-expressing neocortical neurons (red), mounted on the top of a microelectrode array chip (microphotograph: L Petit

Functional repercussions of cortical migration disorders: analysis of DCX knockdown rats

J-B Manent (PI)
with C Cardoso, L Petit, H Becq, I Jorquera, A Carabalona, PPGI
and collaborations with V Crepel and L Aniksztejn teams
In this sub-project, our aim is to identify the seizure-generating structure in DCX knockdown rats, and to describe its properties and connectivity.

 

Key words

Brain development, Epilepsy, Cerebral Cortex, Malformation of Cortical Development, Neuronal Migration, Animal Models

Experimental approaches

Histological and Neuroanatomical Methods, Cellular and Molecular Biology (RNAi interference, in utero electroporation), Cell and Slice Culture, Extracellular Multi-site Recordings with Microelectrode Arrays, Time-lapse Imaging

Collaborators and past memberss

Collaborators:
- Epicure European network (Coordinator G Avanzini)
- Renzo Guerrini (Florence University, Italy),
- Massimo Pasqualetti (Pisa University, Italy)
- Heiko Luhman (Mainz University, Germany)
- Jamel Chelly (Institut Cochin, Paris, France)
- William B. Dobyns (University of Chicago, USA)
- Rikke S. Moller (University of Copenhagen, Denmark)
- Hiroshi Kawasaki (University of Tokyo, Japan)

Past members:
- James Ackman (Yale University)
- Sabrina Khantane (Invitrogen)
- Irina Popova
- Aurélie Carabalona (Columbia University)

Funding

- Communauté Européenne (EC contract number LSH-CT-2006-037315 (EPICURE) FP6 – Thematic priority LIFESCIHEALTH)
- ANR: 2006 neurosciences neurologie et phychiatrie (ANR-06-NEURO-008-01 contract number RPV06055ASA)
- ANR: 2009 Programme Retour Post-doctorants (contract number RPV09010AAA) to JB Manent
- Fondation J Lejeune to JB Manent
- FRC Rotary to A Represa
- Europe/INSERM/Région PACA – PhD fellowship to A Carabalona

Join our team

Our team has open positions for undergraduate students, PhD students and postdoctoral fellows. Applications should be sent to Alfonso Represa.

Publications

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