Investigating mechanisms of activity dependent myelination.

• Applicant: Dr. Sebastian Timmler
• Subject Area: Developmental Neurobiology ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 457783121

Myelination of axons is crucial for central nervous system function. However, not all axons are myelinated, and some are only partially myelinated. What determines whether, and how, an axon is myelinated is unclear. Neuronal activity is an important regulator of myelination, but insufficient to explain discontinuous myelin patterns. I hypothesise that tonic neuronal activity alters the molecular signature and pattern on the axonal surface that render parts of the axon permissive for myelination. I will use a cross-disciplinary approach to identify these molecular changes and characterise new mechanisms of neuron-myelin interaction. I will use optogenetic stimulation to determine specific firing frequencies that enhance myelination in co-cultures. Using these frequencies, I will compare axonal protein expression (molecular signature) in vitro using proteomics and transcriptomics. To track the distribution and localisation (molecular pattern) of candidate proteins, I will apply single-molecule-tracking and two-colour 3D-super-resolution imaging. This mix of straightforward and ambitious experiments will significantly impact our understanding of activity-dependent axon-oligodendrocyte interactions. The proposed work will break new ground in the understanding of myelin plasticity and has the potential to provide novel therapeutic strategies for myelin regeneration in white matter diseases such as Multiple Sclerosis.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Dr. Ragnhildur Thora Karadottir