AsianScientist (Feb. 15, 2018) – A team of scientists from Japan, Singapore and the US has developed a method to deliver light into deep brain tissue, broadening the possibilities for optogenetics studies. They published their findings in Science.
To study brain functions, neurobiologists have relied on a method known as optogenetics, wherein genetically tagged brain cells can be stimulated with light. However, to shine light into the deep recesses of the brain, invasive optical fibers need to be implanted.
In this study, a team of scientists led by Dr. Thomas McHugh at Japan’s RIKEN institute have devised nanoparticles—called upconversion nanoparticles (UCNPs)—which act as a conduit for laser light delivered from outside the skull, thus allowing the non-invasive control of brain activity. These nanoparticles absorb near-infrared laser light and in turn emit visible photons to areas that are inaccessible to standard optogenetics. This method was used to turn on neurons in various brain areas, silence seizure activity as well as evoke memory cells in mice.
“Nanoparticles effectively extend the reach of our lasers, enabling the ‘remote’ delivery of light and potentially leading to non-invasive therapies,” said McHugh.
In optogenetics, blue-green light is used to turn neurons on or off via light-responsive ion channels. Light at these wavelengths, however, scatters strongly and is at the other end of the spectrum from the near-infrared light that can penetrate deeper into brain tissue.
UCNPs composed of elements from the lanthanide family can act as a bridge. Their ‘optogenetic actuation’ turns low-energy near-infrared laser light into blue or green wavelengths for control of specifically labeled cells in the brain. Though such bursts of light deliver considerable energy to a small area, temperature increases or cellular damage were not observed.
In addition to activating neurons, UCNPs can also be used for inhibition, for example to quell experimental seizures in mice. The researchers injected nanoparticles tuned to emit green light into the hippocampus, then energized them with laser pulses at the surface of the skull. Hyperexcitable neurons were effectively silenced in these mice.
In another brain area called the medial septum, nanoparticle-emitted light contributed to synchronizing neurons in an important brain wave called the theta cycle. Furthermore, in mice with learned fear memories, the freezing behavior associated with these experiences was evoked by blue light-emitting UCNPs, also in the hippocampus. Neural activation, inhibition, and memory recall effects were only observed in mice that received nanoparticle-mediated optogenetic stimulation, not in control animals that received laser light without a UCNP injection.
Memory recall in mice also persisted in tests two weeks later. This indicates that the UCNPs remained at the injection site, which was confirmed through microscopy of the brains.
“The nanoparticles appear to be quite stable and biocompatible, making them viable for long-term use. Plus, the low dispersion means we can target neurons very specifically,” said McHugh.
The nanoparticles described in this study are compatible with the various light-activated channels currently in use in the optogenetics field and can be employed for neural activation or inhibition in many deep brain structures. Nanoparticles could become a minimally invasive alternative to optical fibers for brain stimulation, and their chronic interaction with brain tissue is part of ongoing research.
The article can be found at: Chen et al. (2018) Near-infrared Deep Brain Stimulation via Upconversion Nanoparticle–mediated Optogenetics.
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Source: RIKEN; Photo: Shutterstock.
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