This research focuses on the development of a non-invasive/minimally invasive optogenetic technique. The study delves into how visible (VIS) and near-infrared (NIR) light interacts with ex vivo mouse head tissues, highlighting the advantages of the NIR-II biological window for deeper tissue penetration and reduced light absorption and scattering. Our computer simulations and experimental results demonstrated that over 12% of initial light irradiation passes through 1 mm tissue (skin and skull), reaching the brain cortex, potentially enabling minimally invasive neural activation. Moreover, this work reveals the nonlinear optical properties of genetically engineered truncated monomeric and dimeric bacterial phytochromes, demonstrating their photoconversion efficiency of up to 73% in the NIR-II range and potential for optogenetics. This discovery opens new avenues in advanced neurostimulation and biomedical research by enhancing tissue penetration and minimizing invasiveness.
Optogenetic control of neuronal activity requires efficient light energy transmission through head tissues and bone. Here we evaluate the efficiency of ultrashort pulsed and continuous-wave light transmittance through the mouse scalp, skull, and brain tissues in near-IR optical windows. The outcomes of the experiments and computer modelling show that the brain cortex tissues can be exposed to 10-12% of the original laser irradiation. This finding together with the latest discovery of non-linear phytochrome conversion [S.Sokolovski et al. 2021] prove the possibility of phytochrome optogenetics in living animals and may be applied in the future for non-invasive photo-controlling of neural cells.
Optogenetic research has opened up the possibility to control neurons that will help detect and treat neurological diseases in the early stage. Treatment of dysfunctions requires exposure to a partial neural network accessible through the absorption of opsins or phytochromes expressed in the brain matter. The use of II-NIR USP lasers makes it possible to non-linear activate and deactivate photoactuators in neuronal cells through the skull. The possible obstacles for noninvasive stimulation are the limits in light penetration depth, scattering and absorption by biological tissues. This research aimed to investigate light propagation and penetration depth in skin, skull and brain matter of mouse head. To evaluate the light transmittance in brain tissues, we developed an experimental setup with a tunable ultra-short pulsed laser source operating at the wavelength range of 1.1-1.2 μm. This spectrum range corresponds to the spectra of nonlinear absorption of opsins/phytochromes and matches the second biological window where laser irradiation can penetrate the skin and skull bone without damaging and overheating them. The experimental results demonstrate that under certain conditions, the ultra-short pulsed laser radiation can reach a penetration depth with required power that will be sufficient for non-linear activation of opsins/phytochromes in the brain of living animals. These results could support applications of II-NIR USP laser in non-invasive optogenetics, photobiomodulation of the brain functioning and even neurological disorders diagnostics.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.