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

Keywords

Cortex
Epilepsy
plasticity
synaptic transmission
Available to host a PhD student

Publications

Lévi S, Le Roux N, Eugène E, Poncer JC. Benzodiazepine ligands rapidly influence GABAA receptor diffusion and clustering at hippocampal inhibitory synapses. Neuropharmacology. 2015 Jan;88:199-208. doi: 10.1016/j.neuropharm.2014.06.002. Epub 2014 Jun 12.

Benzodiazepine ligands rapidly influence GABAA receptor diffusion and clustering at hippocampal inhibitory synapses. Lévi S, Le Roux N, Eugène E, Poncer JC. Neuropharmacology (2014)

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

Molecular and functional characterization of GAD67-expressing, newborn granule cells in mouse dentate gyrus. Cabezas C, Irinopoulou T, Cauli B, Poncer JC Front. Neural Circuits 7, 60 (2013)

Input-specific learning rules at excitatory synapses onto hippocampal parvalbumin-expressing interneurons. Le Roux N, Cabezas C, Böhm UL, Poncer JC J Physiol. 591, 1809-22 (2013)

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses. Cabezas C, Irinopoulou T, Gauvain G, Poncer JC J Neurosci. 32, 11835-40 (2012)

Role of the neuronal K-Cl co-transporter KCC2 in inhibitory and excitatory neurotransmission. Chamma I, Chevy Q, Poncer JC°, Lévi S° Front. Cell Neurosci. 6:5 (2012)

A human mutation in Gabrg2 associated with generalized epilepsy alters the membrane dynamics of GABAA receptors. Bouthour W, Leroy F, Emmanuelli C, Le Roux N, Carnaud M, Poncer JC & Lévi S Cereb. Cortex 22, 1542-53 (2011)

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

Two novel CLCN2 mutations identified in families with Idiopathic Generalized Epilepsies. Saint-Martin C, Gauvain G, Teodorescu G, Gourfinkel-An I, Fedirko E, Garcia J, Weber YG, Maljevic S, Fahlke C, Nabbout R, Le Guern E, Lerche H, Poncer JC°, Depienne C° Hum Mutat 30, 397-405(2009)

GABAA Receptor Gamma2 Subunit Mutations Linked to Human Epileptic Syndromes Differentially Affect Phasic and Tonic Inhibition. Eugène E, Depienne C, Baulac S, Baulac M, Fritschy JM, LeGuern E, Miles R, Poncer JC J Neurosci. 27, 14108-14116 (2007)

 





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