  Currently, cellular action potentials are detected using either electrical
recordings or exogenous fluorescent probes sensing calcium concentration or
transmembrane voltage. Ca imaging has low temporal resolution, while voltage
indicators are vulnerable to phototoxicity, photobleaching and heating. Here we
report full-field interferometric imaging of individual action potentials by
detecting the movement across the entire cell membrane. Using spike-triggered
averaging of the movies synchronized to electrical recording, we demonstrate
deformations of up to 3 nm (0.9 mrad) during the action potential in spiking
HEK-293 cells, with a rise time of 4 ms. The time course of the
optically-recorded spikes matches electrical waveforms. Since the shot noise
limit of the camera (~2 mrad/pix) precludes detection of the action potential
in a single frame, for all-optical spike detection, images are acquired at 50
kHz, and 50 frames are binned into 1 ms steps to achieve a sensitivity of 0.3
mrad in a single pixel. Using self-reinforcing sensitivity enhancement
algorithm based on iteratively expanding the region of interest for spatial
averaging, individual spikes can be detected by matching the previously
extracted template of the action potential with the optical recording. This
allows all-optical full-field imaging of the propagating action potentials
without exogeneous labels or electrodes.
