https://www.frontiersin.org/articles/10.3389/fnins.2017.00663/full

https://academic.oup.com/scan/article/11/3/387/2375059?login=true

Neuromodulation through magnetism - hmmm....

Lightheadedness?

https://science.sciencemag.org/content/359/6376/679/tab-figures-data

One of the biggest challenges of brain research is how to single out the contribution of a specific neuron types to brain functions and brain disorder states in this ultra-complex network [3], [4]. Ten years ago, a technique called optogenetics was developed, which combines lasers, fiber optics, and genes for light-responsive protein channels called microbial opsins from algae and bacteria to control neural activity precisely in specific nerve cells within whole living brains as animals carry out their daily activities [3].

Briefly, a natural light-sensitive ion-transporting membrane protein (e.g., channelrhodopsin (ChRs), chloride-conducting ChRs (ChloCs)) is expressed in neurons of choice. Shining light to the cells will open the ion channels to generate electrical signals to either stimulate or inhibit neuronal activities. Since the first demonstration of this approach in cell cultures, optogenetics has become the method of choice in neuroscience, which has been successfully applied in many animal models including Caenorhabditis elegans, Drosophila melanogaster, zebrafish, mice, and nonhuman primates [3], [4].

For mammalian models, because of the larger brains that strongly scatter and absorb high energy blue and green lights, insertion of invasive optical fibers is required. Although near infrared laser has been shown to allow deep tissue penetration and induce in vivo stimulation, the depth of this focal excitation is restricted to shallow brain areas because of light scattering. In addition, NIR photons have low energy that is not enough to trigger the light-sensitive ion channels. Thus there is missing link that could connect the NIR to optogenetics to develop noninvasive deep brain stimulation [5]

Chen et al. [5] in Science developed transcranial NIR optogenetic stimulation of specifically labeled neurons in deep brain areas, where tissue-penetrating NIR light is locally converted to visible light by upconversion nanoparticles at levels sufficient for activating neurons (Fig. 1).

The key component in this method is the use of lanthanide-doped upconversion nanoparticles (UCNPs) that are capable of converting low-energy incident NIR photons into high-energy visible blue or green light that could subsequently activate the light sensitive channels expressed on neuronal cells. UCNPs are synthesized by dispersing trivalent lanthanide ions (e.g., Tm3+, Er3+) in dielectric RE-based lattice [5].

They are capable to absorb multiple low-energy photons sequentially in a ladder-like fashion leading to the production of higher energy anti-Stokes luminescence (Fig. 1). The emission wavelength can to be tuned from NIR, visible, to UV range, depending on the type of lanthanide being used. UCNPs offer advantages over organic fluorophores including high resistance to photobleaching and photochemical degradation, which allows UCNPs to be considered as promising new bio-imaging agents, such as single-molecule tracking, multiplexed labeling, and deep tissue imaging [6]. In this study, the UCNPs were implanted in the ventral tegmental area (VTA) of the mouse brain, a region in deep brain located ∼4.2 mm below the skull.

Upon transcranial delivery of 980 nm NIR laser pulses, an upconverted emission with a power density exceeds the level that is sufficient for ChR2 activation. The authors successfully demonstrated the application of in vivo upconversion optogenetics to stimulate dopamine release by activating neurons in the VTA, inhibit neural activity in the hippocampus, or trigger memory recall by targeting NIR excitation to granule cells in the hippocampus.