Signalling pathways controlling rapid astrocyte remodelling in synaptic plasticity and memory formation

• Applicant: Professor Dr. Christian Henneberger
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545084235

Understanding the relationship between function and structure of brain cells and how changes of one affect the other is an important aspect on neuroscience. This does not only apply to neurons and their synaptic connections but also to non-neuronal cells like astrocytes. Recently, a number of important new important discoveries were made regarding astrocyte structure, its changes and the functional implication. New morphological features, organizational principles, mechanisms of morphogenesis were discovered and characterized. Unexpected physiological triggers of astrocyte morphology changes were identified. Also, important new insights are continuously obtained into how their morphology and its changes control their subcellular signaling and neuronal signaling and how that affects complex behaviors We have contributed to this line of research by discovering how induction of long-term potentiation (LTP) of synaptic transmission and of epileptic activity rapidly alters the morphology of hippocampal astrocytes on a time scale of minutes. Two important questions arise from our work: How is the LTP-associated astrocyte remodeling orchestrated by cellular signaling and how does the remodeling affect hippocampus-dependent memory formation. We propose to reveal the astrocytic signaling molecules relevant for these rapid structural changes, the involved remodeling of the astrocytic cytoskeleton, and possibly organelles, and their role in the formation and update of spatial memory. This will be achieved by combining established experimental techniques like multiphoton fluorescence microscopy, electrophysiology, super-resolution expansion microscopy and behavioral tests. Specifically, we will first further optimize the monitoring of astrocyte morphology and then identify the astrocytic signaling molecules that are important for rapid astrocyte remodeling in synaptic plasticity. We will build on these results by revealing how rapid astrocyte remodeling affects their perisynaptic astrocytic processes, their cytoskeleton and the distribution of the astrocytic endoplasmic reticulum and mitochondria. In a final set of experiments, we will identify the specific role of astrocytic remodeling in the formation and update of spatial memory. More generally, the project will uncover the expected mutual dependency of structural changes of astrocytes, hippocampal synapse function and spatial memory.

• DFG Programme: Research Grants