Fiber-optic two-photon optogenetic stimulation.

Optogenetic stimulation of genetically targeted cells is proving to be a powerful tool in the study of cellular systems, both in vitro and in vivo. However, most opsins are activated in the visible spectrum, where significant absorption and scattering of stimulating light occurs, leading to low penetration depth and less precise stimulation. Since we first (to the best of our knowledge) demonstrated two-photon optogenetic stimulation (TPOS), it has gained considerable interest in the probing of cellular circuitry by precise spatial modulation. However, all existing methods use microscope objectives and complex scanning beam geometries. Here, we report a nonscanning method based on multimode fiber to accomplish fiber-optic TPOS of cells.