How Do Glial Cells Sculpt the Assembly and Function of Neural Circuits?
Central nervous system function (CNS) requires precise communication between myriads of neurons and glia. A major challenge is to understand how these different cells organise and influence one another to generate and maintain a functional organ.
We are interested in the communication between neurons and oligodendrocytes, a type of CNS glia. Oligodendrocytes have well established roles in myelinating axons, thereby regulating transmission speed between nerve cells and long-term axonal health. New myelin can be formed almost lifelong throughout development and adulthood, in response to plastic adaptions and to regenerate damaged myelin in disease.
New myelin is formed by the differentiation of specified oligodendrocyte precursor cells (OPCs), which comprise about 5% of all brain cells found throughout the tissue. In fact, there are many more OPCs in the CNS that ever differentiate, and which constantly integrate information from surrounding neurons and other CNS cells. Our group wants to understand how this cell population can be triggered to form new myelin, and how OPCs affect the CNS when they don't form myelin.
a. cell heterogeneity - how do OPCs with different properties contribute to myelin formation?
b. neuron-oligodendrocyte communication - how do OPCs integrate information from neurons?
c. non-canonical OPC functions - how do OPCs affect the CNS when they don't make myelin?
To address these questions, we use a wide range of complementary methods including high resolution microscopy of live cell reporters, optophysiology and biomolecular sensor imaging, cellular genetic manipulations, and behavioural assays. For an overview, read further below, check out our gallery, and look up our publications!
Zebrafish as Model Organism
Our primary model organism for the study of cellular interactions is the zebrafish. Young zebrafish develop rapidly and outside the mother. This makes them easily accessible. Moreover, their small size and optical translucency allow for high-resolution in vivo live cell imaging without the need for any surgical intervention.
High Resolution Microscopy
We use various optical imaging technologies to investigate intercellular communication from the whole organism level down to subcellular structures. Depending on the question, we use point-scanning confocal, two-photon and light-sheet microscopy.
Molecular Genetics
Zebrafish share a high percentage of their genome with that of higher mammalians, including humans. Genetic manipulations allow us to introduce fluorescent reporters to label structures of interest, and to manipulate gene function in a defined cell.
