Non-invasive optical control of endogenous Ca2+ channels in awake mice
Sungsoo Kim, Taeyoon Kyung, Jae‐Hee Chung, Nury Kim, Sehoon Keum, Jinsu Lee, Hyerim Park, Ho Min Kim, Sangkyu Lee, Hee‐Sup Shin, Won Do Heo
Abstract
Abstract Optogenetic approaches for controlling Ca 2+ channels provide powerful means for modulating diverse Ca 2+ -specific biological events in space and time. However, blue light-responsive photoreceptors are, in principle, considered inadequate for deep tissue stimulation unless accompanied by optic fiber insertion. Here, we present an ultra-light-sensitive optogenetic Ca 2+ modulator, named monSTIM1 encompassing engineered cryptochrome2 for manipulating Ca 2+ signaling in the brain of awake mice through non-invasive light delivery. Activation of monSTIM1 in either excitatory neurons or astrocytes of mice brain is able to induce Ca 2+ -dependent gene expression without any mechanical damage in the brain. Furthermore, we demonstrate that non-invasive Ca 2+ modulation in neurons can be sufficiently and effectively translated into changes in behavioral phenotypes of awake mice.