Centres d’intérêts scientifiques
The team tackles 3 major questions:
1) The role of kainate receptors in seizure activities
2) The role of interneurons and the alterations of coding properties in normal and epileptic conditions
3) The role of adhesion molecules involved in neuropathies and seizures
Electrophysiology (local field potential, patch-clamp), calcium imaging, immuno-histochemistry, morphometry, cell biology, cell cultures, virtual reality, genetic animal models.
Synaptopathy, interneurons, adhesion molecules and epilepsy
The team’s objectives are to study the synaptopathy, the role of interneurons and adhesion molecules leading to seizures and hypexcitability. Our studies are conducted at several scales: from the subcellular compartment to the neural microcircuit.
The team has a long history in the study of the physiopathology of Temporal Lobe Epilepsy (TLE), which is one of the most common forms of partial epilepsy in adults. The team has discovered that newly formed synapses between dentate granule cells (DGCs) are not only aberrant in their localization but also in their mode of operation as they operate via a subtype of glutamatergic receptor, the kainate receptor (KAR) not present in naïve conditions (Epsztein et al., 2005). Our studies tackle the impact of ectopic KARs in neuronal coding operation and seizure activity in DGCs in animal models of TLE. For the past ten years, we have obtained several fundamental data demonstrating that network reorganisation and ectopic kainate receptor play a central role in TLE notably by deeply altering the neuronal coding properties leading to different forms of pathological activities including seizures (Epsztein et al., 2010; Artinian et al., 2011, 2015; Peret et al., 2014). We have demonstrated that kainate GluK2/GluK5 receptors expressed ectopically in granular cells of the toothed gyrus play a major role in recurrent TLE seizures (Peret, Christie et al., 2014; Crepel & Mulle, 2014). Based on these data we have published a patent (INSERM Transfer PCT/EP2014/069709 / WO2015036618-A1/N° 10,016,424). The team is now involved in the maturation and development of new antiepileptic approaches targeting these kainate receptors. In this context, the team is a member of the FHU EpiNext.
Our studies also focus on the role of adhesion molecules associated with Kv1 potassium channels and involved in neuropathies with hyperexcitability. In particular, Caspr2 (CNTNAP2) and LGI1 are associated with neurological diseases of autoimmune or genetic origin that generate epilepsy (Canali et al., 2018; Pinatel et al., 2015). We are studying the addressing and molecular architecture of the Kv1 complex, particularly at the initial segment of the axon and Ranvier nodes (Pinatel et al., 2017; Brivio et al., 2017; Hivert et al., 2016). This research programme is approved by the FHU DHUNE
Dr. C Rivera
Dr. R. Khazipov
Dr. R. Cossart
Dr. J. Epsztein
Dr. PP Lenck-Santini
Dr. I. Bureau
Dr. C. Mulle (IINS, Bordeaux)
Pr. F. Bartolomei (Timone Hospital, Marseille)
Pr. D. Scavarda (Timone Hospital, Marseille)
Dr. D. Grimm (University of Heidelberg, Germany)
Dr. Bernard Pirotte (University of Liege, Belgium)
Dr. Domna Karagogeos (University of Crete, Greece)
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