Astrocyte morphology dynamically determines astrocytic Ca2+ signalling

• Applicants: Professor Dr. Christian Henneberger; Dr. Andre Zeug
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Biophysics
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 284079634

Astrocytes are non-neuronal cells in the brain, which can modify the communication of neurons at synapses. Their intracellular Ca2+ signals are known to trigger such changes of synaptic communication. However, the mechanisms that determine the properties of astrocytic Ca2+ signalling are not well understood. One important consideration is the morphology of the astrocyte because any intracellular signal is constrained and shaped by it. Previous work by us and others clearly indicate that indeed astrocytic Ca2+ signalling could be determined by astrocytic morphology and its dynamic changes. In the proposed work, we will investigate this fundamental structure-function relationship in astrocytes in the brain. Our work is based on a large set of established experimental techniques that allow us to modify astrocyte structure using viral vectors, to visualize and analyse astrocyte morphology and its changes, computationally model the effect of those changes on Ca2+ signalling, and to monitor astrocytic Ca2+ signalling and synapse function. In the proposed work, we will first characterize astrocyte morphology and its induced bi-directional changes in general and around synapses, how they modify astrocytic Ca2+ signalling and what the underlying mechanisms are. We will then implement new techniques to quantify additional morphological features (e.g., local surface-to-volume ratios) and for rapid light-induced manipulations of astrocyte morphology. These will then be used to explore how rapid astrocyte morphology changes affect astrocyte Ca2+ signalling and synapse function. These experiments will be performed in cultured astrocyte and astrocytes in acute brain slices and in vivo. Together they will provide new and important insights into astrocyte and brain physiology and fundamental cellular structure-function relationships.

• DFG Programme: Research Grants