A molecular switch between structural brain plasticity and degeneration

Experience changes the brain throughout life. Learning and exercise promote structural brain plasticity, sleep restores structural homeostasis and stressors like isolation, immobility and lack of stimulation drive degeneration. The balance between structural plasticity and homeostasis breaks down in brain disease - psychiatric, neurodegenerative - and aging. I aim to discover the molecular mechanism underlying brain change, its link to neural circuits and behaviour. Building on my discovery of the Drosophila neurotrophin system, I will test the hypothesis that a shared molecular mechanism underlies structural plasticity and degeneration. With genetics, microscopy and imaging, I will test molecules and neural circuits involved. With protein biochemistry, I will identify the critical molecular switch. With behaviour, I will test how stressors modify circuits, and whether identified molecules can reverse degeneration. This work will reveal a molecular and circuit mechanism linking brain plasticity, neurodegeneration and behaviour, to expedite understanding of human brain health.