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