Plasticity in Cortical Networks and Epilepsy

Co-Leaders

Research center

17 rue du Fer à Moulin
75005 Paris

Institution

Inserm
Université Pierre et Marie Curie
ED158
Université Pierre et Marie Curie

Laboratory

Marianne Coutures
Phone: 01 45 87 61 35
UMRS 839
EraNet NEURON (2017-2020)

Keywords

Cortex
Epilepsy
plasticity
synaptic transmission
Available to host a PhD student

Publications

Gauvain G, Chamma I, Chevy Q, Cabezas C, Irinopoulou T, Bodrug N, Carnaud M, Lévi S, Poncer JC (2011) The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines. Proc Natl Acad Sci USA 108:15474-9.

Heubl M, Zang J, Pressey JC, Al Awabdh S, Renner M, Gomez-Castro F, Moutkine I, Eugène E, Russeau M, Kahle KT, Poncer JC, Lévi S (2017) GABAA receptor-dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl--sensitive WNK1 kinase. Nature Communications (in press)

Giralt A, Brito V, Chevy Q, Simonnet C, Otsu Y, Cifuentes-Diaz C, de Pins B, Coura R, Alberch J, Ginés S, Poncer JC, Girault JA (2017) Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model. Nature Communications 8:15592.

Chevy Q, Heubl M, Goutierre M, Backer S, Moutkine I, Eugène E, Bloch-Gallego E, Lévi S, Poncer JC (2015) KCC2 Gates Activity-Driven AMPA Receptor Traffic through Cofilin Phosphorylation. Journal of Neuroscience 35:15772-86.

Chamma I, Heubl M, Chevy Q, Renner M, Moutkine I, Eugène E, Poncer JC, Lévi S (2013) Activity-dependent regulation of the K/Cl transporter KCC2 membrane diffusion, clustering, and function in hippocampal neurons. Journal of Neuroscience  33:15488-503.

 

Fields of research

Neuropharmacology / cell signaling

Research Theme

Cortical GABAergic interneurons play a critical role in shaping the activity of neuronal ensembles. In particular, in the hippocampus, GABA signaling is involved in the maintenance of rhythmic population activities associated with various behavioral states and cognitive tasks.

However, even a partial reduction in GABAergic transmission leads to an anomalous synchronization of neuronal activity and the emergence of epileptiform discharges.

Our objective is to identify the alterations of GABAergic networks responsible for the initiation and maintenance of epileptiform activities in the hippocampal network. Specifically, we combine cellular electrophysiology and molecular imaging techniques to examine:

 - the functional impact of human mutations affecting GABA signaling and associated with idiopathic generalized epileptic syndromes,

 - the long term changes in hippocampal GABAergic circuits initiated by a period of epileptiform activity,

 - the perturbations of chloride homeostasis induced in several pathological conditions, and their long term effects on synaptic transmission in cortical networks,

 - the emergence and the functional consequences of the transient GABAergic phenotype of newborn dentate gyrus granule cells induced upon seizures.

Our work aims at better understanting the consequences of seizures and identify putative targets for novel therapeutical approaches.

Team members

LEVI Sabine
EUGENE Emmanuel
HEUBL Martin
CHEVY Quentin
SCHWARTZ Eric
GOUTIERRE Marie
GOMEZ-CASTRO Ferran

Lab rotation

Targeting chloride homeostasis in temporal lobe epilepsies

Team leader: 

PONCER Jean Christophe

Dates: 

January 2, 2018 - June 29, 2018

Application deadline: 

June 29, 2018

Period

~ Jan-March 2018

~ April-June 2018 (to be discussed)

Project

Temporal lobe epilepsy (TLE) is among the most common forms of complex partial epilepsy and represents about 60% of all epileptic patients. It is often resistant to common antiepileptic drugs and TLE patients may then have no other option than surgical therapy, calling for identification of new therapeutically relevant target.

Our research aims at better understanding the molecular and cellular mechanisms underlying epileptogenesis and we currently focus on deficits in chloride transport that may represent new therapeutic targets in TLE. In this project, we will evaluate the efficacy of various drugs targeting chloride transport on the emergence of epileptiform activities. To this end, we will use multi-electrode array (MEA) recordings of network activity from human brain tissue resected from epileptic patients.

In parallel, in vivo electrophysiological recordings from mouse models will be used to manipulate chloride transporter expression using viral transduction. These experiments will let us test whether altered chloride transporter expression may be causal to TLE and whether drugs targeting these transporters may be beneficial to rescue network activity in TLE patients.

Basic knowledge in electrophysiology would be an asset but is not strictly. 

Contact

Institut du Fer à Moulin - 17 rue du Fer à Moulin 75005 Paris - +33 1 45 87 61 18 - jean-christophe.poncer@inserm.fr

Supervisor: 

PONCER Jean Christophe & GOUTIERRE Marie