Fig 1

Enhanced upconversion efficiency of different kinds of core-shell UCNPs. The upconversion luminescence (a) and the upconversion spectra (b) of core nanoparticles and core/inert-shell nanoparticles 46; The upconversion luminescence (c) and the upconversion spectra (d) of core/inert-shell nanoparticles and core/active-shell nanoparticles 47; The upconversion luminescence (e) and the upconversion spectra (f) of core/active-shell nanoparticles and dye-sensitized core/active-shell nanoparticles 58."

Fig 2

Schematic diagram depicting the generation and application of polymer-UCNP hybrid scaffolds for optogenetic neuronal activation 61."

Fig 3

Modulation of movement behavior in C. elegans by UCNP-mediated NIR optogenetics 62. (a) The C.elegans move fluidly without drastic changes in direction when exposed to NIR light alone (no UCNPs); (b) The C.elegans show a drastic change in direction when exposed to NIR light in the presence of UCNPs; (c) Effect of varying UCNPs concentration on percentage of C.elegans showing reversal phenotype when irradiated with NIR light at 50% duty cycle and peak power 4 W (106 J·cm-2). n = 20 per group; (d) Percentage of C.elegans showing the reversal phenotype upon incubation with UCNPs and subsequent NIR irradiation, along with the controls (untreated C.elegans, C.elegans exposed to NIR light alone, or C. elegans exposed to UCNPs alone). p = 0.0004 between the control and UCNPs + NIR groups. n = 90 per group."

Fig 4

NIR neuromodulation in mice/rats by micro-optrodes containing UCNPs. (a) Schematic of upconversion based neural stimulation and extracellular recording in brains of live animals 64; (b) Representative photograph of the bundle combining a glass UCNPs-Optrode and a metal electrode, which was simultaneously implanted into the visual cortical tissue for upconversion stimulation and electrical recording. Scale bar: 1 mm 64; (c) Raster plots and PSTH (5 ms per bin, 50 trials) showing the temporal correlation between increased spiking activity and NIR illumination in C1V1 animals (30 ms pulse width, 4.4 mW·mm-2). The inset shows typical spiking waveforms 64. (d) Schematic of using NaYF4@NaYF4:Yb/Er@NaYF4 core-shell-shell UCNPs as a transducer to convert NIR irradiation into visible light for inhibiting the activities of neurons expressing eNpHR proteins (top); Power of the emission around 540–570 nm from a device containing UCNPs at various illumination powers of a 980 nm laser (bottom) 67; (e) Representative photograph of the bundle combining a glass UCNPs-based device and a metal electrode with/without 980 nm laser irradiation. Scale bar, 1 mm 67; (f) Raster plots and a PSTH (10 ms/bin, 60 trials) showing the temporal correlation between the decreased spiking activity and the NIR illumination in eNpHR animals (100 ms pulse width, 6 mW·mm-2) 67; (g) Fluorescent images of the operating UCNPs micro-devices (Yb3+-doped) excited by NIR (top). Scale bar, 1 mm. The image of a mouse implanted with a micro-optrode containing UCNPs (bottom). Scale bar, 2 cm 67."

Fig 5

NIR neuromodulation in mice by injecting solution containing UCNPs 68. (a) In vivo experimental scheme for transcranial NIR stimulation of the VTA in anesthetized mice; (b) Confocal images of the VTA after transcranial NIR stimulation under different conditions. Extensive NIR-driven c-Fos (red) expression was observed only in the presence of both UCNPs (blue) and ChR2 expression (labeled with EYFP, green). Scale bars: 100 μm; (c) Percentage of c-Fos-positive neurons within cell population indicated by DAPI (4', 6-diamidino-2-phenylindole), corresponding to the four conditions presented in (B) (n = 3 mice each, F3, 8 = 10.40, P < 0.01); (d) Confocal images of VTA regions at different periods after the injection of silica-coated UCNPs, stained for Iba1 + microglia."

Fig 6

NIR neuromodulation in mice by injecting solution containing lanthanide micro-particles (LMPs) 21. (a) Sites of AAV/LMPs injections (top). Epifluorescence images indicating expression of C1V1-Venus in the mPFC and dorsal striatum (dSTR; middle) and upconversion luminescence from injected LMPs in fixed slices with thicknesses of 100 mm (bottom, illuminated by NIR at a wavelength of 976 nm under a stereomicroscope); (b) Behavior test setup; (c) Locomotor activity of mice under repeated irradiation with 10 ms NIR light pulses at 10 Hz. Red bars indicate the timing of NIR irradiation. Top: injection into the mPFC; bottom: injection into the dSTR. Data are shown as mean ± SEM; *p < 0.05 and ***p < 0.001, unpaired Student's t test."