{"id":22373,"date":"2018-02-12T23:31:59","date_gmt":"2018-02-12T23:31:59","guid":{"rendered":"http:\/\/www.kurzweilai.net\/?p=308752"},"modified":"2018-02-14T18:06:54","modified_gmt":"2018-02-14T18:06:54","slug":"how-to-shine-light-deeper-into-the-brain","status":"publish","type":"post","link":"https:\/\/hoo.central12.com\/fugic\/2018\/02\/12\/how-to-shine-light-deeper-into-the-brain\/","title":{"rendered":"How to shine light deeper into the brain"},"content":{"rendered":"
\"\"

Near-infrared (NIR) light can easily pass through brain tissue with minimal scattering, allowing it to reach deep structures. There, up-conversion nanoparticles (UCNPs; blue) previously inserted in the tissue can absorb this light to generate shorter-wavelength blue-green light that can activate nearby neurons. (credit: RIKEN)<\/p><\/div>\n

An international team of researchers has developed a way to shine light at new depths in the brain. It may lead to development of new, non-invasive clinical treatments for neurological disorders and new research tools.<\/p>\n

The new method extends the depth that\u00a0optogenetics — a method for stimulating neurons with light — can reach. With optogenetics, blue-green light is used to turn on “light-gated ion channels” in neurons to stimulate neural activity. But blue-green light is heavily scattered by tissue. That limits how deep the light can reach and currently requires insertion of invasive optical fibers.<\/p>\n

The researchers\u00a0took a new approach to brain stimulation, as they reported in\u00a0Science\u00a0<\/em>on February 9.<\/p>\n

    \n
  1. They used longer-wavelength (650 to 1350nm)\u00a0near-infrared (NIR) light, which can penetrate deeper into the brain (via the skull) of mice.<\/li>\n
  2. The NIR light illuminated “upconversion nanoparticles” (UCNPs), which absorbed the near-infrared laser light\u00a0and glowed blue-green in\u00a0formerly inaccessible (deep) targeted neural areas.*<\/li>\n
  3. The blue-green light then triggered (via chromophores, light-responsive molecules) ion channels in the neurons to turn on memory cells in the hippocampus and other areas. These included the medial septum, where nanoparticle-emitted light contributed to synchronizing neurons in a brain wave called the theta cycle.**<\/li>\n<\/ol>\n
    \"\"<\/a>

    Non-invasive activation of neurons in the VTA, a reward center of the mouse brain. The blue-light sensitive ChR2 chromophores (green) were expressed (from an injection) on both sides of the VTA. But upconversion nanoparticles (blue) were only injected on the right. So when near-IR light was applied to both sides, it only activated the expression of the activity-induced chromophore cFos gene (red) on the side with the nanoparticles. (credit: RIKEN)<\/p><\/div>\n

    This study was a collaboration between scientists at the RIKEN Brain Science Institute, the National University of Singapore, the University of Tokyo, Johns Hopkins University, and Keio University.<\/p>\n

    Non-invasive light therapy<\/strong><\/p>\n

    \u201cNanoparticles effectively extend the reach of our lasers, enabling \u2018remote\u2019 delivery of light and potentially leading to non-invasive therapies,\u201d says\u00a0Thomas McHugh<\/a>, research group leader at the\u00a0RIKEN<\/a>\u00a0Brain Science Institute in Japan.\u00a0In addition to activating neurons, UCNPs can also be used for inhibition.\u00a0In this study,\u00a0UCNPs\u00a0were able to quell experimental seizures in mice by emitting yellow light to silence hyperexcitable neurons.<\/p>\n

    \"\"

    Schematic showing near-infrared radiation (NIR) being absorbed by upconversion nanoparticles (UCNPs) and re-radiated as shorter-wavelength (peaking at 450 and 475 nm) blue light that triggers a previously injected chromophore (a light emitting molecule expressed by neurons) — in this case, channelrhodopsin-2 (ChR2). In one experiment, the chromophore triggered a calcium ion channel in neurons in the ventral tegmental area (VTA) of the mouse brain (a region located ~4.2 mm below the skull), causing stimulation of neurons. (credit: Shuo Chen et al.\/Science)<\/p><\/div>\n

    While current deep brain stimulation is effective in alleviating specific neurological symptoms, it lacks cell-type specificity and requires permanently implanted electrodes, the researchers note.<\/p>\n

    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.\u00a0\u201cThe 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,\u201d says McHugh.<\/p>\n

    However, \u201ca number of challenges must be overcome before this technique can be used in patients,\u201d say Neus Feliu et al. in \u201cToward an optically controlled brain, Science\u00a0<\/em>\u00a009 Feb 2018<\/a>. \u201cSpecifically, neurons have to be transfected with light-gated ion channels \u2026 a substantial challenge [and] \u2026 placed close to the target neurons. \u2026 Neuronal networks undergo continuous changes [so] the stimulation pattern and placement of [nanoparticles] may have to be adjusted over time. \u2026 Potent upconverting NPs are also needed \u2026 [which] may change properties over time, such as structural degradation and loss of functional properties. \u2026 Long-term toxicity studies also need to be carried out.\u201d<\/p>\n

    * \u201cThe lanthanide-doped up-conversion nanoparticles (UCNPs) were capable of converting low-energy incident NIR photons into high-energy visible emission with an efficiency orders of magnitude greater than that of multiphoton processes. … <\/em>The core-shell UCNPs exhibited a characteristic up-conversion emission spectrum peaking at 450 and 475 nm upon excitation at 980 nm. Upon transcranial delivery of 980-nm CW laser pulses at a peak power of 2.0 W (25-ms pulses at 20 Hz over 1 s), an upconverted emission with a power density of ~0.063 mW\/mm2 was detected. The conversion yield of NIR to blue light was ~2.5%. NIR pulses delivered across a wide range of laser energies to living tissue result in little photochemical or thermal damage.<\/em>\u201d —\u00a0Shuo Chen et al.\/Science<\/p>\n

    ** \u201cMemory 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.\u201d\u00a0—\u00a0Shuo Chen et al.\/Science<\/em><\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

     <\/p>\n

    \n

    Abstract of\u00a0Near-infrared deep brain stimulation via upconversion nanoparticle\u2013mediated optogenetics<\/em><\/h4>\n

    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.<\/p>\n","protected":false},"excerpt":{"rendered":"

    An international team of researchers has developed a way to shine light at new depths in the brain. It may lead to development of new, non-invasive clinical treatments for neurological disorders and new research tools. The new method extends the depth that optogenetics — a method for stimulating neurons with light — can reach. With optogenetics, […]<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[49,43],"tags":[],"class_list":["post-22373","post","type-post","status-publish","format-standard","hentry","category-cognitive-scienceneuroscience","category-news"],"_links":{"self":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/22373"}],"collection":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/comments?post=22373"}],"version-history":[{"count":2,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/22373\/revisions"}],"predecessor-version":[{"id":22405,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/22373\/revisions\/22405"}],"wp:attachment":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/media?parent=22373"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/categories?post=22373"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/tags?post=22373"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}