Expertise and current research performed: Charite Universitätsmedizin Berlin is the best publishing Medical school in Germany with particular strength in Neuroscience, Immunology and Infectiology, Cardiovascular Research, Molecular Biology and Genetics. The Institute of Neurophysiology focuses on developmental neurobiology of the visual system, physiology and pathophysiology of the amygdale and thze hippocampus. The Neurosciences are supported by 4 grants funded by the Sonderforschungsbereich (Center Grant Program) from the Deutsche Forschungsgeminschaft and 2 grants funded by the Federal Ministry of Education, Research and Technology. The Institute of Neurophysiology is currently involved in 13 projects in different Center grants (the usual size of center grants varies between 9 and 18 projects), with a particular contribution to the Transregional Center Grant on Mesial Temporal lobe epilepsies, together with the University of Bonn. The group also directs a graduate college (a grant from the Deutsche Forschungsgeminschaft) on cellular mechanisms of learning and memory consolidation in the hippocampal formation. The group actively cooperates with research units in Bonn, Paris and Helsinki and produces common publications. The following research themes are relevant to this project:

- Physiological interactions between the entorhinal cortex and hippocampus and disturbances in Epilepsy

- Role of different interneurones in generation of Theta, Gamma and high frequency oscillations

- Consequences of blood brain barrier opening

- Mechanisms underlying cell death in status epilepticus

- Mechanisms underlying pharmacoresistance of human TLE

Facilities/Equipment: The Institute is equipped with different fluorescence imaging set ups for studies on living cells, confocal microscope, 2 patch clamp infrared video microscopy set ups for studies on visually identified cells expressing GFP three interface set ups for studies on human tissue and slices from animals with spontaneous receurrent seizures , video EEG for identifying spontaneous seizures, histology. A mini-Pet, a 7T MRI rat scanner and two photon confocal microscopy are available for animal studies.

Personnel involved in the project

Principal investigator: Uwe Heinemann (M). Prof Dr med, Head of Institute since 1993, 1986-1993: Assoc.Prof. Inst. Neurophysiology, University Cologne, Development of in vitro seizure models, kindling epilepsy, 1981-1986 Heisenberg Fellow, MPI Psychiatry Munich Analysis of Ca concentration changes in chronic epilepsy models. 1973 – 1980 Postdoc, Habilitation, Studies on ion homeostasis in neocortex. Research interests: Mechanisms of epileptogenesis; coupling of neuronal and metabolic activity in normal and epileptic tissue, Mechanisms of pharmacoresistance, generation of network oscillations.

Tengis Gloveli (M) 1992 – present: Research assistant; 1980 -1992 Senior Lecturer University Tiblisi, Georgia, Working in the field since 1992. Research interests. Identification of functions of GABAergic neurones in rhythmogenesis in normal and epileptic hippocampus, Interactions between entorhinal cortex and hippocampus. Siegrun Gabriel (F). Researcher since 1993 Studies on glial cell function and network reorganisation in chronic epileptic tissue studies on phamracoresistance in human epileptic tissue. Before Research assistant Studies on geniculate fiunctions in rats. Behrens Christoph (M) Dr. med. Neurophysiology. Research assistant since 2001, Studies on network oscillations in normal and chronic epileptic tissue and on mechanisms underlying generation of sharp wave riplle complexes. Claudia Boehlen (F). PhD student. Master in Neurobiology 2005, PhD Thesis on: Membrane oscillations and resonance in identified hippocampal interneurones. Ekaterina Kipriani (F). Master in Biology, Univerity of Tiblisi 2003 Thesis on Interactions between inhibitory interneurones. Master in Neurobiology 2005, PhD Thesis on: Membrane oscillations and resonance in identified hippocampal interneurones. Katrin Schulze (F). Dr rer nat. Technician. Degree in Biology 1995, Induction of epilepsy, monitoring of animals, histology and immune histochemistry, cell culture. Thomas Sander, (M). Dr. (MD). Senior scientist. Head of the neurogenetics group. He has a long track record in molecular genetic studies on common IGE syndromes. Thomas Sander is an experienced epileptologist and molecular geneticist. His expertise also comprises biostatistical methods of linkage and linkage disequilibrium mapping. Anne Gehrmann, (F) biologist. Research interests: neurobiology of signal transduction, molecular genetics of epilepsy. Carolin Engel (F), research technician. Nadine Wittstruck, (F) research technician. Peter Wolf, (M) Danish Epilepsy Centre. M.D. Professor of epileptology at the Danish Epilepsy Centre and the National Hospital in Copenhagen. Previously, medical director of Bethel Epilepsy Centre, Germany. Working in the field since around 1975. Research interests within many areas of epileptology. The Danish Epilepsy Centre, Dianalund is the only epilepsy hospital in Denmark. Patients are received from the whole country, and most patients are difficult to diagnose, classify or treat. Christian Hansen (M) M.D., medical director at the Danish Epilepsy Centre, Dianalund. Working in the field of epileptology since 1999. Main research interest is the genetics of epilepsy. Moeller Rikke (F). Ph.D. student. Master of biomedicine. Main research interest is genetics of epilepsy. Ulrich Stephani (M), University Hospital, Kiel. Prof. Dr. (medicine), director of the Department of Neuropediatrics and director of the epilepsy centre for children and adolescents at University of Kiel (both since 1992). Working in pediatric epileptology since 1989. Research interests are: Clinical, neurophysiologic and (molecular) genetic characterisation and therapy of epilepsy syndromes and other paroxysmal disorders. Treatment studies in epileptology. Neurophysiology of headache/migraine. The Department of Neuropediatrics and the associated Epilepsy centre for children and adolescents is the reference center in the field of non-surgical pediatric and adolescent epileptology and other paroxysmal disorders in Northern Germany. Since about five decades clinical and molecular genetics in epileptology concerning epilepsy syndromes and electroencephalography are the major focus. A large family cohort with different epilepsy phenotypes and EEG-endophenotypes has been collected and carefully recorded (incl. storage of DNA samples of the family members). Specific activities deal with functional MRI in combination with EEG in patients with focal epilepsies. Mark Gardiner (M), University College London. MB BCh (1972). Professor of Paediatrics at UCL from 1991. Working in field of molecular genetics since 1986. Research interests in molecular genetics of inherited disorders of childhood onset with a focus on neurogenetics including genetics of epilepsies and neuronal ceroid lipofuscinoses. Two PhD students should be identified.

Recent relevant publications/patents

1.        Behrens CJ van den Boom LP, de Hoz L, Friedman A and Heinemann U. (2005) Induction of sharp wave-ripple complexes in vitro and reorganization of hippocampal networks. Nature Neuroscience (in press).

2.        Gloveli T, Dugladze T, Rotstein HG, Traub RD, Monyer H, Heinemann U, Whittington MA and Kopell NJ. (2005) Orthogonal arrangement of rhythm generating microcircuits in the hippocampus. Proc Natl Acad Sci U S A.

3.        Gabriel S, Njunting M, Pomper JK, Merschhemke M, Sanabria ER, Eilers A, Kivi A, Zeller M, Meencke HJ, Cavalheiro EA, Heinemann U, Lehmann TN (2004) Stimulus and potassium-induced epileptiform activity in the human dentate gyrus from patients with and without hippocampal sclerosis. J Neurosci. 24 (46):10416-30.

4.        Gloveli T, Behr J, Dugladze T, Kokaia Z, Kokaia M, Heinemann U. (2003) Kindling alters entorhinal cortex-hippocampal interaction by increased efficacy of presynaptic GABA(B) autoreceptors in layer III of the entorhinal cortex. Neurobiol Dis. 13 (3):203-12.