In Vivo Optical Clearing of Mammalian Brain
Talei Franzesi, G.; Gupta, I.; Hu, M.; Piatkveich, K.; Yildirim, M.; Zhao, J.-P.; Eom, M.; Han, S.; Park, D.; Andaraarachchi, H.; Li, Z.; Greenhagen, J.; Islam, A. M.; Vashishtha, P.; Yaqoob, Z.; Pak, N.; Wissner-Gross, A. D.; Martin-Alarcon, D.; Veinot, J.; So, P. T.; Kortshagen, U.; Yoon, Y.-G.; Sur, M.; Boyden, E. S.
Show abstract
Established methods for imaging the living mammalian brain have, to date, taken the brains optical properties as fixed; we here demonstrate that it is possible to modify the optical properties of the brain itself to significantly enhance at-depth imaging while preserving native physiology. Using a small amount of any of several biocompatible materials to raise the refractive index of solutions superfusing the brain prior to imaging, we could increase several-fold the signals from the deepest cells normally visible and, under both one-photon and two-photon imaging, visualize cells previously too dim to see. The enhancement was observed for both anatomical and functional fluorescent reporters across a broad range of emission wavelengths. Importantly, visual tuning properties of cortical neurons in awake mice, and electrophysiological properties of neurons assessed ex vivo, were not altered by this procedure.
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