Abstract
Microbial rhodopsins widely used for optogenetics are sensitive to light in the visible spectrum. As visible light is heavily scattered and absorbed by tissue, stimulating light for optogenetic control does not reach deep in the tissue irradiated from outside the subject body. Conventional optogenetics employs fiber optics inserted close to the target, which is highly invasive and poses various problems for researchers. Recent advances in material science integrated with neuroscience have enabled remote optogenetic control of neuronal activities in living animals using up- or down-conversion phosphors. The development of these methodologies has stimulated researchers to test novel strategies for less invasive, wireless control of cellular functions in the brain and other tissues. Here, we review recent reports related to these new technologies and discuss the current limitations and future perspectives toward the establishment of non-invasive optogenetics for clinical applications.
Highlights
For advancing the understanding of brain function and dysfunction, both observation and perturbation of the activities of well-defined neuronal circuits are required
Using a highly light-sensitive step-function channelrhodopsin 2 (ChR2) variant, it is possible to activate neurons at the depth of several millimeters with transcranial blue light stimulation (Gong et al, 2020). This approach needs a substantial duration of light stimulation with a high intensity (∼400 mW/mm2 at the fiber tip; Gong et al, 2020) to achieve sufficient neuronal activation, creating issues of time resolution and tissue heating. We focus on another attempt to overcome the issues of optic fiber implantation, introducing recent studies showing the feasibility of using phosphor particles that emit visible light in response to illumination of further-reaching electromagnetic waves such as near-infrared (NIR) light and X-rays
Recent advances in material science integrated with neuroscience have made it possible to achieve remote optogenetic control of neuronal activity in living animals
Summary
For advancing the understanding of brain function and dysfunction, both observation and perturbation of the activities of well-defined neuronal circuits are required. This approach needs a substantial duration of light stimulation (tens of seconds) with a high intensity (∼400 mW/mm2 at the fiber tip; Gong et al, 2020) to achieve sufficient neuronal activation, creating issues of time resolution and tissue heating. Such NIR-mediated remote optogenetics can be extended to behavioral experiments using mice with implantation of an optic fiber on the skull (Figure 1F; Chen et al, 2018).
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