Recent developments for two-photon fiberscope to enable neural imaging in freely-behaving rodents under nearly natural conditions

Ultracompact ultra-lightweight two-photon (2P) fiberscopes enable real-time functional neuroimaging in freely-behaving rodents, allowing investigation of how head-mounted weight and rotational resistance affect neuronal activity. We developed a levitation system to counteract head-mounted weight and a proactive optoelectrical commutator with real-time torque sensing and feedback control to eliminate rotational constraints. Neuroimaging revealed that both factors influence the overall activity of a non-negligible population of neurons, highlighting the need to study neural networks under near-natural conditions. Furthermore, we demonstrated a focus-tunable 2P fiberscope integrating a miniature compound deformable lens, expanding the capability of 2P fiberscopy in neuroscience and potential clinical applications.