  Optogenetics has emerged as an exciting tool for manipulating neural
activity, which in turn, can modulate behavior in live organisms. However,
detecting the response to the optical stimulation requires electrophysiology
with physical contact or fluorescent imaging at target locations, which is
often limited by photobleaching and phototoxicity. In this paper, we show that
phase imaging can report the intracellular transport induced by optogenetic
stimulation. We developed a multimodal instrument that can both stimulate cells
with high spatial resolution and detect optical pathlength changes with
nanometer scale sensitivity. We found that optical pathlength fluctuations
following stimulation are consistent with active organelle transport.
Furthermore, the results indicate a broadening in the transport velocity
distribution, which is significantly higher in stimulated cells compared to
optogenetically inactive cells. It is likely that this label-free, contactless
measurement of optogenetic response will provide an enabling approach to
neuroscience.
