Label-free optical imaging of membrane potential

Offering high temporal resolution, voltage imaging is an important and essential technique in neuroscience. Among different optical imaging approaches, the label-free approach remains attractive due to its unique value coming from free of exogenous chromophores. The intrinsic voltage-indicating signals arising from membrane deformation, membrane spectral change, phase shift, light scattering, and membrane hydration haven been reported. First demonstrated 70 years ago, label-free optical imaging of membrane potential is still at an early stage and the field is challenged by the relatively small signals generated by the intrinsic optical properties. We review major contrast mechanisms used for label-free voltage imaging and discuss several recent exciting advances that could potentially enable membrane potential imaging in mammalian neurons at high speed and high sensitivity.