Myelin plasticity in the adult and aged brain: A cross-species approach (360G-Wellcome-320009_Z_24_Z)

The adult brain’s capacity to adapt and acquire new skills diminishes with age. Historically, learning was understood to be primarily driven by neuronal changes, while myelin was considered static. My research in humans and rodents has revealed myelin’s unexpected yet critical role in memory and motor learning. Key questions that remain are how brain activity regulates myelination to support learning and whether interventions targeting myelin can improve cognitive-motor function as we age. A cross-species approach will be used to answer these questions. This program will uncover mechanisms that modulate myelin-proxies in the living human brain by employing functional and structural magnetic resonance imaging (MRI) methods at ultra-high field. We will pharmacologically drive myelination in older adults and test effects in motor and memory tasks and in brain metrics. In parallel, we will establish causal relations with performance in similar tasks in aged transgenic mice by ablating or stimulating production of new myelin. Combining mouse models and MRI will help identify sensitive imaging markers for specific myelin dynamics, facilitating translation into further human studies. This work will advance our comprehension of how myelin plasticity relates to circuit activity during adulthood and uncover novel targets to enhance healthy ageing through myelin modulation.