Research Report 2010 - MDC

Pathophysiological Mechanisms of Neurological and Psychiatric DisordersStructure of the GroupHelmut KettenmannGroup LeaderProf. Dr. Helmut KettenmannScientistsDr. Anika Bick-SanderDr. Rainer GlassDr. Katrin FaerberDr. Vitali MatiashDr. Christiane Nolte (part time)Dr. Daniel Reyes-HaroCellular NeurosciencesOur goal is to understand the role of glial cells in physiology and pathology. We focus onquestions as to how neuronal activity is sensed by astrocytes, how astrocytes communicateamong each other, and how they feedback on neurons. A second focus addresses the role ofconnexin proteins in oligodendrocytes function, the cells which are the myelin forming cells inthe brain. Thirdly, we study the expression of transmitter receptors in microglial cells and howactivation of these receptors influences microglial function. This is of particular interest withinthe context of pathology and we are currently studying this question in stroke and gliomas. Afourth line of research addresses the question as to how glioma cells interact with the intrinsicbrain cells, specifically microglia and stem cells. We are aiming to understand this interaction ona molecular level, in particular with the hope of identifying tools which impair glioma invasion.The central nervous system contains two major cellpopulations, neurons and glial cells. The neurons areregarded as the elements mediating the electricalactivity in the brain. As a consequence, neuroscienceresearch of the past has focused on this cell type. Thefunctional role of glial cells is not as obvious: while theywere first described as cells providing only structuralsupport to neurons, a series of more recent studies onglial cell function has attracted the attention of theneuroscience community. It has become evident thatglial cells are essential for the proper functioning of thebrain. The different types of glial cells fulfil distincttasks. Oligodendrocytes are the myelin-forming cells ofthe central nervous system and ensure a rapid signalconduction in the white matter. The role of astrocytes isless well defined; they provide guiding structures duringdevelopment and represent important elements forcontrolling the composition of the extracellular spacemediating signals between the brain endothelium andthe neuronal membrane. They form intimate contactwith synapses and neuronal activity results in astrocyteresponses. Microglial cells are immuno-competent cellsin the brain and their functional role is best defined asthe first responsive elements during pathologic events.The present research program is focused on four topics:(1) the role of astrocytes in information processing (2)the impact of connexion expression for oligodendrocytesfunction (3) the response of microglial cells tobrain injury and (4) the interaction of gliomas withmicroglia and stem cells.Mechanisms of neuron-astrocyte interactionsThis project aims to understand signaling mechanismsbetween astrocytes and neurons. We recently havefocused on two preparations, the barrel cortex and themedial nucleus of the trapezoid body. The Calyx of Heldis a giant glutamatergic terminal on the principal neuronsin this nucleus. It has been used as a modelsynapse to study mechanisms of transmitter releaseand synaptic plasticity since both, pre- and postsynapticelements can be simultaneously recorded using physiologicaltechniques. We have studied the morphologicalarrangements and the properties of the astrocyteswhich are in close contact with the Calyx. We use brainslices containing the medial nucleus of the trapezoidbody and have established to simultaneously record178 Function and Dysfunction of the Nervous System