Research Report 2010 - MDC

Graduate StudentsLarisa BulavinaBruno BenedettiGiselle CheungSridhar ChirasaniMinChi KuJitender KumarJochen MüllerMarta MaglioneJulia ParnisStefanie SeifertKristin StockGrietje TessmannKatyayni VinnakotaTechnical AssistantsBrigitte Gerlach (part time)Irene HauptKarin Heufelder (part time)Regina PiskeNadine Scharek (part time)Michaela Seeger-ZografakisFigure 1. Stereological counting ofmicroglial cells in the dentate gyrus ofB6/129svj mouse. Microglia are stained withanti-Iba1 antibodies and visualized withDAB (Olympus, 100x). Nuclei are counterstainedwith toluidine blue.from neurons and astrocytes. We obtained evidencethat two types of astrocytes perceive the Calyx activity.One type of astrocyte is characterized by a complexmembrane current pattern and these cells receivesynaptic input mediated by glutamate. The other typeof astrocyte characterized by a passive membrane currentpattern exhibits currents which are due to glutamateuptake. Ultrastructural inspection revealed thatboth types of astrocytes are in direct contact with both,the pre- and postsynaptic membrane. Moreover, wecould identify glial postsynaptic structures on the cellwith complex current pattern. One goal of this study isto determine how astrocytes integrate synaptic inputfrom defined synapses (funded by a Schwerpunktprogrammof the DFG).The sensory input of the whiskers in rodents is representedin the somatosensory cortex. Each whisker projectsinto a defined cortical area, the barrel field. Theseareas are morphologically delineated and can be recognizedin acute brain slices without additional staining.The barrel cortex is a well established model for plasticitysince removal of whiskers results in changes of thebarrel fields. After stimulation in the cortical layer 4, theinput to the barrel field, we can record responses inastrocytes and in neurons by using Ca 2+ imaging andpatch-clamp recording. While the neuronal activityspreads beyond barrel borders, the astrocyte activity isrestricted to the barrel field. We are now particularlyinterested in the question how astrocyte activity feedsback on neuronal activity. In an ongoing study we try toperturb astrocyte function while simultaneouslyrecording neuronal activity.How does connexin expression affect oligodendrocytefunction?In a collaboration with Prof. Klaus Willecke’s group inBonn we are studying the expression of connexins, themolecular substrate for gap junctions in oligodendrocytes.Gap junctions are communication channelsbetween cells which allow the exchange of moleculesbetween cells, but also serve for intercellular signaling.They can also connect different compartments within agiven cell. By using different combinations of mouselines with connexion deletions, we determine which ofthe connexins are essential to form gap junctionsamong oligodendrocytes and among astrocytes andoligodendrocytes. This also has an important clinicalimpact. Mutations in connexins expressed by oligodendrocytescan lead to defects in myelin formation, animportant function of oligodendrocytes. We are currentlystudying a mouse mutant which mimics apatient mutation which leads to leukodystrophy. WeFunction and Dysfunction of the Nervous System 179