Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics

Abstract

Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.

Biocompatible and Implantable Optical Fibers and Waveguides for Biomedicine

“…Implantable light sources, such as light emitting diodes and cell-based lasers [13,14,15], have been demonstrated for biomedical applications. Besides, injectable upconversion optoelectronic devices [16] or nanoparticles [17] have been developed to expand the optical penetration depth. However, these active implantable light sources still demand for further optimization to realize practical and clinical uses considering their sophisticated fabrication methods and biocompatibility issues.…”

Extended Near-Infrared Photoactivity of Bi6Fe1.9Co0.1Ti3O18 by Upconversion Nanoparticles

“…Therefore, the extended utilization of sunlight from Vis to NIR light is an attractive issue for developing photocatalysts. On the other hand, upconversion materials could convert low-energy NIR light into high-energy UV or Vis light through a nonlinear optical process [28,29,30,31,32,33]. Furthermore, compared with conventional fluorescent materials, such as organic dyes and quantum dots, upconversion nanoparticles have the following advantages: (i) High photostability and chemical stability; (ii) low toxicity to the human body; (iii) good biocompatibility by surface modification and functionalization; and (iv) good optical transparency over a wide wavelength range and low phonon energy [34,35,36,37].…”

Nanoparticle-Mediated Upconversion of Near-Infrared Light: A Step Closer to Optogenetic Neuromodulation in Humans

“…However, lanthanide-doped upconversion nanoparticles can convert low-energy near-infrared photons to high-energy visible emission [18]. In their study, Chen et al [16] injected an adeno-associated virus (AAV) encoding channel rhodopsin-2 (a nonspecific cation channel) as well as NaYF4:Yb/Tm nanocrystals coated with silica in the mouse ventral tegmental area. Transcranial continuous-wave near-infrared laser pulses were sufficient to reach nanocrystals, which upconverted the signal to blue emission (optimal wavelengths to activate channel rhodopsin-2).…”

“…In a recent ground-breaking article published in the Science February 2018 edition, Chen et al [16] validated a method for near-infrared DBS via upconversion nanoparticle-mediated optogenetics, offering the potential for minimally invasive optogenetic neu­romodulation [17]. Previous attempts at deep brain optogenetics relied on the implantation of optical fibers or light-emitting diodes (LEDs) [1, 2].…”

“…Light intensity can only be safely increased to a certain level, over which it causes neuronal damage through overheating [12, 13]. Near-infrared wavelengths (650–1,350 nm) show the highest depths of penetration due to substantially less absorption from hemoglobin, myoglobin and lipid, but fail to consistently activate light-reactive channels [13, 16]. However, lanthanide-doped upconversion nanoparticles can convert low-energy near-infrared photons to high-energy visible emission [18].…”