Institut National de la Sante Et de la Recherche Medicale (France)

CR2 INSERM - Institut National de la Sante Et de la Recherche Medicale (France)

Prof. Michel Baulac, phone +331 4216 1811, Fax +331 4424 5247, michel.baulac@psl.ap-hop-paris.fr

INSERM is a reference institution in France in the field of development of new therapeutic agents in pediatric diseases.

In the frame of the EPICURE project, the following units will participate and represented by this partner:

- INSERM U751 “Epilepsy and Cognition”, FACULTE DE MEDECINE TIMONE, Marseille

Among this units, the Unit 739 will act, only from an administrative point of view, as partner with the European Commission. For this purpose, Prof. Michel Baulac will be the person in charge for EPICURE representing the INSERM.

Dr. Richard Miles, phone +331 4077 8165 Fax +331 4077 8167, rmiles@chups.jussieu.fr

Prof. Michel Baulac, phone +331 4216 1811, Fax +331 4424 5247, michel.baulac@psl.ap-hop-paris.fr

Expertise and current research performed: INSERM U739 directed by Richard Miles, focuses on cellular and synaptic physiology in relation to the generation of epileptiform activities in human, tissue, animal models of the epilepsies and postgenomic studies on the effects of mutations associated with hereditary epilepsies. They have examined how unitary synaptic interactions contribute to the emergence of synchronous actities, and threshold phenomena in cellular firing and population synchrony. Techniques to record epileptiform activities of human tissue and to examine the functional effects of mutations associated with hereditary epilepsies have been developed. This research takes place in a context of epilepsy research at the CHU Pitié-Salpêtrière directed by Michel Baulac. The work includes: (1) Epilepsy genetics: familial forms, phenotyping, genotyping; (2) Functional post genomic studies of the mutations; (3) Neurophysiology of post operative tissue (physiology of pace maker epileptic cells in human epileptic hippocampus); (4) Brain imaging: correlations with epileptogenic zone; (5) Clinical trials of new antiepileptic drugs; (6) Cognitive consequences of hippocampal lesions; (7) Anticipation of epileptic seizures by non linear analysis of EEG signal.

Facilities/Equipment: Six set-ups are available for electrical recordings from brain slices, cell cultures or freely moving animals, using whole cell or sharp electrode and multi-unit and EEG recording techniques. Human epileptic tissue is available with full patient consent and ethical committee approval at about one operation per week. An imaging system for high-quality anatomical studies as well as facilities for molecular biological work based on facilities for cell and slice culture and transfection will be available for the project. One set-up for recording from freely moving animals and one in vitro setup will be used for experiments on the genetics of febrile seizures in SP2. Three in vitro setups will be used for work in SP3 when human tissue is available

Principal investigator: Richard Miles (M). PhD Bristol 1981. Director of the INSERM U739. Research interests in how cells and synapses shape pathological population activities such as the epilepsies. Worked with RKS Wong and RD Traub to integrate data on unitary excitatory and inhibitory synaptic interactions in computer simulations of epileptiform activites. Explored the anatomy of synaptic connections with Tamas Freund (CR5-MTA KOKI). He has developed extracellular techniques to measure activity in small neuronal ensembles and detected interictal-like and ictal-like activity in tissue from human epileptic patients.

Michel Baulac (M). Professor of Neuroanatomy and Neurology at Univ Paris VI. Heads a clinical department at the Pitie-Salpetriere Hospital. Chairman of the Commission on European Affairs of the International League against Epilepsy. Prof. Baulac has developed a comprehensive epilepsy programme over 20 years which now includes EEG video-monitoring, in- and out-patient clinics, epilepsy surgery and clinical pharmacology of antiepileptic drugs. He coordinates research at the Pitié-Salpêtrière on seizure anticipation based on non-linear mathematical models, genetics of epilepsy, and neuroimaging and neuroanatomical characteristics of epilepsy. Stéphane Clemenceau (M). MD 1993. Neurosurgeon. PH Hospital Practioner Dépt Neurochirurgie, CHU Pitié-Salpêtrière. Since 1995 has operated to excise tissue from epileptic patients with pharmaco-resistant epilepsies of the temporal lobe. The surgical techniques of Dr. Clemenceau assure an excellent quality of neuronal tissue needed for the proposed experiments. Desdemona Fricker (F). PhD 2000 Univ Paris VI. Researcher in the INSERM unit U739 since 2002. Research interests in the properties and plasticity of intrinsic cellular currents that govern cellular excitability. In this project she will focus on Cl-currents in neurons of human tissue slices and animal models of the epilepsies. Kathryn Richards (F). PhD 2000 Brandeis Univ. MA. Postdoctoral researcher in the INSERM unit U739 since 2004. Research interests in molecular and physiological approaches to neuronal identity. In this project she will follow whole cell and RT-PCR analyses of Na-K-ATPase and other molecules regulating homeostasis in neurons of human tissue and animal models of the epilepsies. Vincent Navarro (M). MD, Neurologist. Ph.D. Paris VI 2004. Research interests in EEG video monitoring and signal analysis, as well as detection of pre ictal state in in vivo microelectrode records. In this project will focus on in vivo EEG-video records of febrile seizures in wild-type animals and those with mutations of familial epilepsies. Gilles Huberfeld (M). MD 2001 Neurologist. PhD student., Univ Paris VI. Will be involved in recordings from human tissue in this project and liaise with clinical departments. Emmanuel Eugene (M). MSc 1991, CNAM, Paris. INSERM ingenieur since 1995. Research interests in microscopy, with special expertise in confocal imaging. In this project he will work on the morphological analysis on receptors and transporters expressed in human epileptic hippocampus. Charlotte Boccara (F). MSc 2005 Univ Paris VI. PhD student. Mechanisms of febrile seizures in vitro and in vivo. Benoit Crepon (M). MD, neurologist. Thesis work on recordings from microelectrodes in human partial epilepsies. Post Doc to be hired: Céline Dinocourt (F). Univ Maryland, US, she is an excellent morphologist who has worked on human tissue and developed models of epilepsy in slice cultures is a good candidate for this post. Dr Isabelle Gourfinkel-An (F). Senior neurologist, specialised in epilepsy, with specific competences in adolescents, rare epileptic diseases and genetics of epilepsy. She is the clinician involved in all the epilepsy gene discovery studies conducted at la Pitié-Salpêtrière University Hospital

1. Prida LM, Huberfeld G, Cohen I & Miles R (2005) Threshold behaviour in the initiation of population bursts in the hippocampus. Neuron (in press).

2. Cohen I, Navarro V, Clemenceau S, Baulac M & Miles R. (2002) on the origin of interictal activity in human temporal lobe epilepsy in vitro. Science 298, 1418 - 1421.

3. Baulac S, Huberfeld G, An-Gourfinkel I, Mitropoulou G, Béranger A, Prud'homme JF, Baulac M, Brice A, Bruzzone R, & Le Guern E. (2001) First genetic evidence of GABAA receptor implication in epilepsy: a mutation in Gamma2 subunit gene. Nature Genetics, 28, 46-8.

4. Fricker D & Miles R (2000) Differences between EPSP - spike transduction in pyramidal and inhibitory cells of the hippocampus. Neuron 28, 559-569.

5. Parra P, Gulyas AI & Miles R (1998) How many subsets of inhibitory cells in the hippocampus? Neuron 20, 983-993.

Catherine Chiron, ph. +33 1 42 19 27 00, fax +33 1 42 19 28 74, catherine.chiron@nck.aphp.fr

Expertise and current research performed: The assessment of new antiepileptic drugs (AED) in severe and genetically sustained disease such as Severe Myoclonic Epilepsy in Infancy (SMEI), is one of the fields of excellence of INSERM. The specific activities of INSERM/Unit 663 and collaborators are to develop new strategies of AED trials in specific epilepsy syndromes which are drug resistant in young children. The group has a great experience of national and international multicenter trials in this field and have collaborated since more than 10 years with numerous European teams interested in the same field. The current research activities of the INSERM/U663 are to study the impact of brain maturation on the epilepsy phenotypes using AED trials in relation with nosology, functional imaging, neuropsychology, and genotype. The group designed, coordonated and performed the first multicenter controlled trials in infantile epilepsies (Chiron et al 1997 and 2000). It developed new strategies of trials with small numbers of patients (Chiron et al, in press), the dosages of the new AEDs in children (Rey et al, 2004), and the study of CYP and PGP and their relevant polymorphisms (Tran et al 1997). The group is also involved in the genetic of epilepsies (Nabbout et al 2003), in new animal models of epilepsy in developing brain (Quilichini et al 2003), in ethics of pediatric trials (Amann et al 2001), in new pharmacokinetic approaches (“population”) in pediatrics and coordinates two of the first AED controlled trials in very young children.

Facilities/Equipment: The INSERM/U663 is equipped with the clinical environment labelled for drug trials in children. It is also administratively and technically closed to the pharmacology department where the dosages of drugs and molecular biology of genetic polymorphisms are performed.

Principal investigator: Catherine Chiron (F). MD, PhD. Director of Research at INSERM. Director of the Research Unit (INSERM U663) on “Pediatric Epilepsies and Brain Plasticity”. Member of the Commission de Pharmacovigilance of the French Agency (AFSSAPS). Working in the field since 1985. Research interests are: AED trials in children, Functional cerebral imaging in childhood epilepsy, Epilepsy in developing brain.

Olivier Dulac (M). MD. PUPH. Head of the clinical department of Neurology and Metabolism in Hospital Necker, Paris. Member of the Research Unit INSERM U663. Member of the Commision of Drugs in the ILAE (International League against Epilepsy). Working in the field of antiepileptic drugs (AED) trials in children since 1976. Research interests are: Epilepsy in children, Classification of Epilepsies, AED trials in children, Genetics of Epilepsies, Cognitive development and neuropsychology of childhood epilepsy. Rima Nabbout-Tarantino (F). MD, PhD. PH clinical department of Neurology and Metabolism in Hospital Necker, Paris. Member of the Research Unit INSERM U663. Working in the field since 1994. Research interests are: Genetics in Epilepsy, AED trials in children. Valérie Diologent (F). ARC (Clinical Research Assistant). Technician in the Research Unit INSERM U663. Contractual agent at INSERM. Working in the field since 2005. Research interests are: AED treatment in childhood Epilepsy, AED trials in children. Gerard Pons (M). MD, PhD. PUPH. Head of the department of Clinical Pharmacology in Hospital Cochin-Saint Vincent de Paul, Paris. Member of the pediatric working party of EMEA. Working in the field of antiepileptic drug (AED) trials in children since 1984. Research interests are: innovative methodologies in clinical trials in children, AED trials in children, modelisation of pharmacokinetics and of PK/PD approaches of AEDs in children, influence of maturation on AED metabolism in children, influence of pharmacogenetics on AED metabolism, transport and target response. Agnes Tran (F). PharmD, PhD. University assistant in the department of Clinical Pharmacology in Hospital Cochin-Saint Vincent de Paul, Paris. Working in the field since 1994. Research interests are: AED metabolism, pharmacogenetics. Vincent Jullien (M). PharmD, PhD. University assistant in the department of Clinical Pharmacology in Hospital Cochin-Saint Vincent de Paul, Paris. Working in the field since 2003. Research interests are: modelisation in PK/PD relationship. Mireille Cammas (F). Technician in the department of Clinical Pharmacology in Hospital Cochin-Saint Vincent de Paul, Paris. Working in the field since 1980. Research interests are: drug metabolism, pharmacogenetics. Jean-Marc Treluyer (M). MD, PhD. Head of the Unit of Clinical Research (URC) in Hospital Cochin-Saint Vincent de Paul, Paris. Working in the field since 1996. Research interests are: trials in children, innovative methodologies in trials.

1. Quilichini,P.P. (2003) Effects of antiepileptic drugs on refractory seizures in the intact immature corticohippocampal formation in vitro. Epilepsia 44, 1365-1374.

2. Nabbout,R. (2003) Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology 60, 1961-1967.

4. Chiron,C. (2000) Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. Lancet 356, 1638-1642.

5. Chiron,C. (1997) Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res 26, 389-395.

Prof. Yehezkel Ben-Ari, ph. +33 491828100, fax. +33491828101, ben-ari@immed.univ.mrs.it

Expertise and current research performed: INMED/INSERM U29 is the reference centre in the fields of Neuroscience and Epilepsy in France. INMED mainly deal with physiology and pathophysiology of the developing brain, including epilepsy and brain ischemia. The specific activities of INMED are electrophysiological and imaging studies of neuronal and network activities in vitro and in vivo experimental animal models, physiology of synaptic transmission, role of neurotransmitters GABA and glutamate in development and developmental pathologies. The current research activities of INMED include: involvement in research projects on (i) characterization of the immature patterns of activity in the developing cortex, cellular and network mechanisms of their generation, identification of pacemakers and physiological roles of the early activities; (ii) on the mechanisms underlying ictogenesis and epileptogenesis in the immature brain including mirror focus formation, role of high frequency oscillations, receptors and ionic transporters; (iii) on the long-term consequences of neonatal seizures. INMED develops in vitro and in vivo preparations to investigate the physiological and pathological function of neuronal networks and imaging techniques and analytical tools for dynamic study of network activities.

Facilities/Equipment: INMED is equipped with: Culture room (incubators, hoods, etc); Histology lab (vibratomes, cryostats, fluorescence microscope, binoculars, etc); 10 electrophysiology (patch clamp, infrared, fluorescence) set-ups; Molecular biology lab (PCR, electrophoresis, etc); Time-lapse video-microscope set-up; 3 electrophysiology (patch clamp, infrared, fluorescence) set-ups; 2 biphoton microscopes (Trimscope equipped with a patch-clam set-up and Zeiss LSM); Confocal microscope (Olympus); Animal facilities, transgenic mices; Electroporator, gene gun, pico-spritzer and micromanipulator; Electron microscopy lab with two microscopes and ultramicrotomes; 2 extracellular recording set-ups

Principal investigator: Yehezkel Ben-Ari (M). PhD., Founder and Director of the Mediterranean Institute of Neurobiology (Marseille). Over 450 publications in peered review international journals. Amongst the 100 most Highly cited researcher according to ISI. Research interests: reactive synaptogenesis in epileptic and postischemic tissue, development of the central nervous system, Synapse activity, network activity. Electrophysiology, patch-clamp, Morphology and cell imaging expertises.

Alfonso Represa (M). MD, PhD. paediatrician, Directeur de Recherché INSERM. Past positions: Assistant Professor, Valladolid university (Spain)(1980-1986). Associated professor, Dept of Anatomy, University of Calgary (AB, Canada) (1996-1997). Working at the INSERM U29 since 1986. Research interests are: reactive synaptogenesis in epileptic and postischemic tissue, development of the central nervous system, neuronal migration modulation and migration defaults. Morphology and cell culture expertises. Carlos Cardoso (M). PhD in 1999, PostDoc fellow at the laboratory of Dr. David Ledbetter (human genetics dept., Chicago University, USA; 2000-2001). Research position at the INSERM since 2001. Research interest: human Genetics, clinical research, mental retardation cortical dysplasias. Isabel Jorquera (F). Technician at INSERM. Research interests: anatomical studies of cortical neurons and networks, neuronal reconstructions, epilepsy, development. Rustem Khazipov (M). Dr. MD, PhD. Directeur de Recherché INSERM. Past positions: Assistant Professor, Kazan Medical University (1991), Research fellow, Harvard Medical School (2001-2002), Associate in Neurology, Dartmouth Medical School (2002-2003), Visiting Professor, Rutgers University (2003). Working in the field since 1991. Research interests are: physiology and pathophysiology of development of the central nervous system, synaptic transmission, cortical neuronal networks, GABA, epilepsy, hypoxia. Rosa Cossart (F). PhD. Chargé de Recherches CNRS. Past positions: 2001-2002 HFSP postdoctoral fellow at Columbia University (Pr.Yuste Laboratory). Trained in Mathematics (Ecole Centrale Paris 1997). Expert in two-photon imaging. Working in the field since 1998. Research interests are: Cortical networks-GABAergic networks-Epilepsy-Development-Kainate receptors. Valerie Crepel (M). PhD. Research position at INSERM. Research interests are: physiology and physio-pathology of development of the central nervous system, synaptic transmission, cortical neuronal networks, kainite receptors, brain ischemia, epilepsy. Laurent Aniksztejn (M). PhD. Research position at INSERM. Research interests are: physiology and physio-pathology of development of the central nervous system, synaptic transmission, cortical neuronal networks, glutamate transporters, epilepsy. Jean-Luc Gaiarsa (M). PhD. Research position at INSERM. Research interests are: physiology and physio-pathology of development of the central nervous system, synaptic transmission, GABA, plasticity at GABAergic synapses, early patterns of activity, epilepsy. Diabira Djabe (M). Technician at INSERM. Research interests: physiological studies of cortical neurons and networks, epilepsy, development. Nadine Ferrand (F). Technician at INSERM. Research interests: anatomical studies of cortical neurons and networks, neuronal reconstructions, epilepsy, development. Helene Becq Clot-Faybesse (F). PhD. Ingénieur d’étude à l’INSERM. Research interests are: physiology and pathophysiology of development of the central nervous system and study of different types of migration in the brain. Zilberter Yuri (M). PhD Director of Research INSERM. Research interests are: physiology and physio-pathology of the cortical netwroks, synaptic transmission, paired recordings for connected pyramidal cells and interneurons, synaptic plasticity, epilepsy. Khalilov, Ilgam (M). PhD. Charge de Recherché INSERM. Past positions: Chercheur Post-doctoral à l’INSERM U29 France (1995-2005). Working in the field since 1984. Research interests are: physiology and pathophysiology of development of the central nervous system, synaptic transmission, GABA, epilepsy. Minlebaev Marat (M). Dr. M.D., Ph.D. in Normal Physiology. Present position: Researcher in INMED/INSERM U29. Past positions: Assistant Professor, Kazan Medical University (2001-present). Working in the field since 1996. Research interests are: physiology and pathophysiology of development of the central nervous system, synaptic transmission, cortical neuronal networks, GABA, epilepsy, hypoxia.). Milh Mathieu (M). MD, Actual position: PhD student. Past position that are relevant for EPICURE: Neuropediatrician. Pediatric Epileptologist working in the field since 2001. Research interests are: physiology and pathophysiology of development of the central nervous system and epilepsy. Epsztein Jerome (M). Actual position: PhD student. Research interests are: physiology of synaptic transmission, kainite receptors, hypoxia, epilepsy. Manent, Jean-Bernard (M). PhD student. Working on modulation of neuroblasts migration through the activation of GABA and glutamate receptors. Study of the effects of antiepileptics on neuronal migration. Development of experimental models to investigate cell migration. Pellegrino Christophe (M). Technician at INSERM. Research interests: in vitro studies of cortical neurons and networks, development, molecular biology, transfection-infection of maturing neurons

1. Khazipov, R. (2004) Early motor activity drives spindle-bursts in developing somatosensory cortex. Nature, 2004, 432: 758-761.

2. Khalilov, I. et al. (2003) In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures. Nature Neuroscience 6, 1079-85.

3. Cossart, R. et al. (2003) Attractor dynamics of network UP states in the neocortex. Nature, 423, 283-288.

4. Leinekugel, X. (2002) Correlated bursts of activity in the neonatal hippocampus in vivo. Science, 296, 2049-52.

5. Demarque et al. (2002) Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation. Neuron 36, 1051-1061.

Dr. Christophe Bernard, ph. +33 (0)4 91 29 98 06, fax +33 (0)4 91 78 99 14, christophe.bernard@medecine.univ-mrs.fr

Expertise and current research performed: The team is a world reference centre in the field of adult epilepsy. The group deals with: epileptic patient exploration (high resolution EEG, MRI, fMRI, PET, MEG), presurgical evaluation (+ depth EEG), neurosurgery (invasive resections and Gamma knife), animal models of temporal lobe epilepsy. The specific activities are: explore the mechanisms underlying seizure genesis and propagation in patients with electrophysiological techniques (collaboration with INSERM U642) and imaging (collaboration with INRIA, CEMEREM, IFR31 and UCL London); explore the mechanisms underlying seizure genesis and propagation in animal models using in vitro and in vivo electrophysiology and functional morphology (collaboration with UCLA, Instituto Cajal, Hungarian Academy of Science). The current research activities involve: the localization of the epileptogenic zone in patients and experimental models, how different structures bind or co-operate at seizure onset, the relationships between ictal and interictal activities, the mechanisms underlying the genesis and propagation of ictal and interictal activities, the rules of reorganization of the networks involved in ictal and interictal activities, the identification of new therapeutical targets, the assessment of the cognitive consequences of ictal and interictal activities, the development of non invasive techniques for diagnosis and presurgical evaluation, the development of an imaging platform (MEG, fMRI, tractography).

Facilities/Equipment: The laboratory is equipped with 1 research MEG, 3 research MRI, 3 depth EEG recording devices, 5 high resolution EEG devices, 2 in vitro electrophysiology rigs (equipped with infrared and fluorescence), 1 Neurolucida platform (for 3D reconstruction), 1 video-EEG monitoring device for rodents and all the necessary equipment for functional morphology and electrophysiology.

Principal investigator: Christophe Bernard (M). PhD. Directeur de Recherche 1 INSERM. Past positions: Assistant Professor (Baylor College of Medicine, Houston, TX, 1999-2001). Working in the field since 1992. Research interests are: organization and reorganization of neuronal networks, synaptic transmission, GABA, epilepsy, interneurons, potassium and calcium channels, dendrites, information processing, modelling.

Monique Esclapez (F). PhD. Chargé de Recherche 1 INSERM. Working in the field since 1989. Research interests are functional morphology, epilepsy, GABA, interneurons. Laetitia Chauvière (F). PhD student (1^st year). Research interests are epilepsy, synaptic transmission, synaptic integration, potassium channels.

1. Bernard C., Gozlan H., Milh M., Morozov Y, Freund T. & Ben-Ari Y. Altering cannabinoid signaling during development disrupts neuronal activity. PNAS. 102, 1388-1393.

2. Bernard C., Anderson A., Poolos N., Becker A., Beck H. & Johson D. (2004) Acquired dendritic channelopathy in epilepsy. Science. 305, 532-535.

3. Cossart R., Dinoncourt C., Hirsch J.C., Ben-Ari Y., Eesclapez M. & Bernard C. (2001) GABAergic inhibition in temporal lobe epilepsy: more in somata, less in dendrites. Nature Neuroscience. 4, 52-62.

4. Cossart R., Esclapez M., Tyzio R., Dinoncort C., Hirsch J.C., Ben-Ari Y. & Bernard C. (2001) Presynaptic kainate receptors that enhance quantal release of GABA on CA1 hippocampal interneurons. Neuron 29, 497-508.

5. Hirsch J.C., Agassandian C., Merchan A., Ben-Ari Y., De Felipe J., Esclapez M. & Bernard C. (1999) Deficit of GABA quantal release in temporal lobe epilepsy. Nature Neuroscience. 2, 499-500.

Expertise and current research performed: The specific activities of the team are: -phenotype-genotype correlations in collaboration with the epilepsy centre at la Pitié-Salpêtrière hospital (Dr I. An and Pr. M. Baulac) and the service of child neurology at Necker-Les Enfant Malades Hospital (Dr. R. Nabbout and Pr. O.Dulac); -localisation and identification of new genes; -gene expression studies at mRNA or protein level; -recombinant technologies involved in cellular or animal models; -development of cellular and animal models (rodents); -RNA interference. The work is devoted to the characterization of familial forms of epilepsy. 1) Genetically determined association of epilepsy and febrile seizures- Linkage; identification of genes; study of the functional consequences of mutations in the GABA_A receptor in hippocampal cultures and in a conditional transgenic mice; 2) Homeostasis of chloride ions in epilepsy by genetic and biological approaches: mutation screening of ClCN2 and others candidate genes; molecular and cellular consequences of RNAi against ClC2 and KCC2; 3) Identification of genes responsible for autosomal recessive epilepsies-phenotyping; linkage; identification of genes. 4) Search for mutations in LGI1 and caracterization of the functional consequences of the mutations.

Facilities/Equipment: The INSERM Unit 679 is equipped with: For moleular biology: 7 thermocyclers, a 3730 ABI sequencer, an ABI real-time PCR apparatus, a lab for recombining technologies and a lab for radioactivity; For cellular biology: 2 L1 and 2 L2 labs, 4 microscopes with fluorescence and 3 inverted microscopes, each with image analysis systems; facilities to perform experiments on rodents.

Principal investigator: Dr. Eric LeGuern (M). MD, PhD. Head of the neurogenetics laboratory since 2000, La Salpêtrière hospital; Head of the research group of inherited neuropathies and epilepsy (INSERM unit U679) since 1996, La Salpêtrière hospital, Paris, France. Professional experience : 1993-1997: assistant in cellular biology, Paris VI University and in Neurology, La Pitié-Salpêtrière hospital; 1998-2004: Senior Lecturer in Medical genetics, Paris VI university and Hospital practician, Department of Genetics, La Pitié-Salpêtrière hospital, Paris, France. Research interest: genetics of inherited neuropathies and familial epilepsies.

Dr. Stéphanie Baulac (F). PhD. researcher position since 2005. Professional experience : 1998-2001: PhD occupation and Teaching assistant position at the Pitié-salpêtrière hospital, Paris, France; 2002-2005, post-doctoral occupation at the Harvard Medical School, Boston, USA; Since 2005, research position at the Pitié-salpêtrière hospital, Paris, France. Research interest: genetic and physiopathological aspects of familial epilepsies. Dr. Christel Depienne (F). Assistant professor in medical genetics, Department of genetics, La Pitié-Salpêtrière hospital, Paris since 2002; Professional experience : 1997-2000: PhD student at the medical research department, CEA (Atomic Energy Center), Fontenay-aux-roses, France; 2000-2001: Post-doctoral Fellow in the Molecular Genetics Center, Gif/Yvette, France; 2001-2002: Post-doctoral Fellow at the Functional Genomics Department, SANOFI-SYNTHELABO, Rueil-Malmaison, France. Research interest: genetics and functional aspects of neurodegenerative disorders and epilepsy. Cécile Saint-Martin. (F) PhD student. Master degree in neurosciences. Research interests: genetic regulations of Chloride homeostasis. Institution: ministry of research. Nicole Ravisé. (F). Research engineer. Licence in biotechnology. Research interests: molecular and cellular biology of inherited neuropathies and epilepsy. Working in the field since 1991. Institution: INSERM. Estelle Fédirko. (F). Basic Scientist. Licence in biotechnology. Research interests: molecular and cellular biology of epilepsy. Working in the field since 2004. Institution: “Assistance Publique des hopitaux de Paris” (Paris Hospital). Two technicians will be hired.

1. Escayg A.*, Baulac S.*, Moulard B.*, et al. (2000) Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nature Genetics 24:343-5. (*equal contribution)

2. Baulac S, et al. (2001) First genetic evidence of GABA_A receptor dysfunction in epilepsy: a mutation in the Gamma 2 subunit gene. Nature Genetics 28:46-8.

3. Nabbout R, et al. (2002) A locus for simple pure febrile seizures maps to chromosome 6q22-q24. Brain; 125: 2668-2680.

4. Nabbout R, et al. (2003) Absence of mutations in major GEFS+ genes in myoclonic astatic epilepsy. Epilepsy research 56: 127-33.

5. Gourfinkel-An et al. (2004) Monogenic epilepsies. Lancet Neurology 3: 209-218.