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Systems Biology of the Synapse in Mental Disorders

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Systems Biology of the Synapse in Mental Disorders Systems Biology of the Synapse Prolog communicational meetings between theoreticians Psychiatric disorders are based on a dysfunction of such as systems scientists, computational scientists in Mental Disorders synapses in neural networks. For schizophrenia and and empirical researchers such as addiction among others the dopamine and glutamatergic neuropsychiatrists and neurobiologists. We started synapses are of relevance, for depression the with a workshop with Arvid Carlsson and th 5 International Workshop on norepinephrine and the serotonin synpase are more discussed his models of networks of Computational Neuropsychiatry important. In dementia e.g. the deficiency of the schizophrenia. In 2006 we organized a second cholinergic system is treated by anticholinergic workshop in order to discuss clinical and th th May 8 /9 2009 substances. All diseases can be treated by changing the experimental data and theoretical concepts of Department of Psychiatry synaptic transmission by molecular switches such as disturbances of the working memory as they are Alzheimer Saal receptor blockade or reuptake blockers by blockade of observed in patients with schizophrenia. In 2007 Nussbaumstrasse 7 enzymatic degradation of transmitter etc. indicating that we discussed the perspective of Molecular Munich not only the synaptic molecular mechanisms but also the Systems Biology on schizophrenia. In 2008, we electrophysiological properties might be modulated. In applied these experiences on addiction. many cases the significant treatment effects have a We want to discuss if theoretical neuropsychiatry latency of about 10 days. Although important progress is has essential benefits by using the tools of systems Transmitter Signal of presynaptic cell made in treatment of mental disorders, still the science like systemic modeling and computer D-2- Transporter psychopharmacological treatment is not satisfying simulations. Autoreceptor especially regarding side effects. Calcium This is showing that we do not understand the dynamics Felix TRETTER, Margot ALBUS (IAK-KMO) D-1- D1 of pathology and reorganization of synapses. Dan RUJESCU (Univ. of Munich) receptor postsynaptic D-2-receptor D2 Membran of For this reason the dynamics of various components of Peter GEBICKE-HAERTER (Univ. Mannheim) denrite of Adenylatcyclase postsynaptic cell Signal of postsynaptic cell synaptic transmission should be studied: The kinetics of Hans BRAUN (Univ. of Marburg) control of synthesis, storage, release, reuptake, Walter E. MÜLLER (Univ. of Frankfurt) degradation, receptor occupation, up-regulation, and Isar Amper Clinics down-regulation. Contact: F. Tretter Clinic Munich East (FRG) Additionally, the synapses have to be related to the Phone: ++49-89-4562-3708 neuron as the basic functional unit of the brain. This Fax: ++49-89-4562-3754 Department of Psychiatry perspective corresponds to the molecular biological Email: [email protected] University of Munich (FRG) research approach that now is integrating more and more the view of systems biology. Systems biology aims to Department of Pharmacology reconstruct the cell on the basis of molecular biological Registration (no registration fee): University of Mannheim (FRG) data. This “bottom-up” reconstruction is based on [email protected] quantitative kinetic data that are integrated in Physiological Institute mathematical models that are transformed into Supported by: University of Marburg (FRG) computerized models. By these models “in-silico”- Essex, experiments can be performed that help to understand Bristol-Myers-Squipp, Department of Pharmacology complex networks of chemical pathways. BioSim, EU-Network of Excellence University of Frankfurt (FRG) It seems to be helpful for understanding the dynamics and the pathology of synapses by computational models. Institute of Bioinformatics and Systems Biology With this aim we started a series of workshops on Helmholtz Zentrum München (FRG) “Computational Neuropsychiatry” in order to relate psychiatry to computational modeling in theoretical neuroscience in 2005. These workshops are designed as ----------- Friday May 8 -------------------- ----------- Saturday May 9 ------------------ 17:05 Coffee Break 13:30 Opening 9:00 Dan RUJESCU, Felix TRETTER, Margot ALBUS, Felix TRETTER, Dan Introduction – more details RUJESCU, Peter GEBICKE Moderation: Michael KOCH (Univ. of Bremen, FRG) HAERTER, Hans BRAUN, Walter MÜLLER 17:20 Peter ERDI (Complex Systems, Kalamzoo College, Moderation: Hans-Werner MEWES USA) (Bioinformatics, Helmholtz, Munich, FRG) Multi-scale modelling approach to schizophrenia as a 9:15 Eberhard VOIT (Georgia Institute of 13:45 Introduction - Psychiatry, the Synapse dysconnection syndrome Technology, Georgia, USA) and Systems Biology A systemic model of dopamine synthesis. Felix TRETTER, Eduardo MENDOZA Intracellular dopamine signalling network (Psychology, Physics, Univ. of Munich) 18:05 Discussion 10:00 Discussion Moderation: Hans BRAUN (Univ. of Marburg) Moderation: Walter E. MÜLLER (Pharmacology, Univ. Moderation: Uwe AN DER HEIDEN 14:15 Ingo VERNALEKEN (Psychiatry, Univ. of of Frankfurt, FRG) (Mathematics, Univ. of Witten, FRG) Aachen, FRG) 18:20 Andreas DRAGUHN (Physiology, Univ. of 10:15 Wolfgang HAUBER (Physiology, Stuttgart) The synaptic action of antipsychotic drugs – Heidelberg, FRG) Intrasynaptic Dynamcis of transmitters up-regulation after receptor blockade by No simple switch - the complex functions of chemical antipsychotics? synapses. 10:45 Discussion 11:00 Coffee Break 14:45 Discussion 18:55 Discussion Moderation: n.n. 15:00 Coffee Break 11:15 Svetlana POSTNOVA (Neurodynamics, Moderation: Oliver POGARELL (Univ. of Munich) Univ. Marburg, FRG) 19:15 Evening lecture A neuronal model of homeostatic processes: Moderation: Dan RUJESCU (Univ. of Munich) Henry MARKRAM (Brain-Mind Institute Lausanne, CH) Activity dependent modulation of synaptic 15:20 Anthony GRACE (Psychiatry, Univ. of The Blue Brain Project: Modelling synapses in a transmission Pittsburgh, USA) cortical column The signalling properties of dopamine networks 11:45 Discussion and schizophrenia 20:00 Discussion Moderation: Georg WINTERER (Psychiatry, 20:15 End of the Session Univ. of Düsseldorf) 16:05 Discussion 12:00 Hans LILJENSTRÖM (Biophysics, Univ. of Uppsala, Sweden) Modelling the synapse in networks Moderation: Peter GEBICKE-HAERTER (Centre for Mental Health, Mannheim, FRG) 12:30 Discussion 16:20 Bita MOGHADDAM (Psychiatry, Univ. of 12:45 General Discussion & Conclusions Pittsburgh, USA) Dan RUJESCU, Felix TRETTER The circuitry of glutamate synapses and 13:30 End of the Session schizophrenia 2 .
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