Recent advances in two-photon imaging techniques have revolutionized neuroscience by enabling long-term, minimal-invasive monitoring of neuronal structures and activities in cellular and subcellular resolution in live animals. Contrary to conventional interpretations that neural hardwiring is determined in early life; new evidence suggests that in the adult brains, neural circuits constantly undergo re-wiring. In the motor system, re-organization of neural hardwiring is more prominent during motor learning. However, it is unknown how newly learned skills are incorporated into existing neural circuits without affecting the exsisting. The molecular mechanisms underlying this re-organization remain elusive and the causality of neural circuits rewiring and their function in motor learning and in PD is still largely unknown.
To address this question, which extends across molecular, cellular, and behavioral levels, it requires approaches combining several state-of–the-art technologies. We conduct a top-down approach, with mice as the model system. These techniques, including multiphoton microscopy, patch-clamp electrophysiology, and microwire bundle and CMOS multielectrode array (MEA), for monitoring morphology and activity of a single synapse to a large neuronal population in mice. We also use cell-type- and neural circuit-specific optogenetic and chemogenetic manipulation, and deep-learning-based motion tracking to study mouse behaviors. We aim to bridge our understanding between molecular, cellular, and systems level mechanisms underlying motor learning and dysfunction.