Neuron: Deep optogenetic control of the brain without implants

May 26, 2020 /
BiovalleyBIOON// According to a report in the journal Neuron, scientists have created an optical-sensitive visual protein that is so sensitive that it reacts to external light stimuli even when implanted into cells deep in the tissueExperiments in mice and macaques showed that emitted blue light on the skull or brain surface was enough to activate neurons that expressed visual proteins at a depth of six millimeters"It's even possible, and that's what surprised me, " said Gregory Corder of the University of Pennsylvania, who studies the neurological basis of pain and addiction, who wasn't involved in the studyHe continued, "At that depth, basically, any part of the rodent brain can do this non-invasive technique..Very impressiveAdriana Galvan, a neuropathy expert at theYekis National Primate Research Center, added: "This advance will help to expand the use of photo
geneticin non-human primate models and bring the technique closer to clinical use in humans." "Galvan is not a member of the research team eitherimage source: GUOPING FENG
lightgeneticis an exciting cell, such as neurons, that can be controlled at random by lightTo do this, the researchers genetically engineered cells to produce an ion channel called a visual protein, which is located on the cell membrane and opens with a specific wavelength of lightTurn on the lights and let the ions fill the cells, causing them to glow Because light is less likely to penetrate tissue, researchers previously inserted fiber optic cables into the brain to activate neurons deep in the brains of living animals that produce visual proteins It's "highly intrusive," Galvan said, explaining that "brain tissue can be destroyed." "
therefore, researchers are working on ways to reduce the genetic of light One way is to adjust the visual proteins to make them more sensitive to light, or to make them react to red light, which is easier to penetrate human tissue than blue light -- traditionally the protein reacts to the wavelength of blue light When The Massachusetts Institute of Technology's Guoping Feng and his team developed their new visual protein, proposing a non-invasive photo-occurrence strategy was not a priority for them He said it was "a bit of a surprise." at the time, Feng was using another adjusted visual protein called the Step Function Vision Protein (SFO), which is designed to be turned on in response to one wavelength and kept until it is turned off by another wavelength But the SFO is not very sensitive, Feng explains, so his team decided to introduce a mutation that is thought to increase sensitivity in another visual protein Feng said the effect was much better than expected "At first, I was like, 'Oh, we're done, we screwed up,'" he recalls 'SFO is very sensitive, and when the animal is under any strong light source, the neurons start to discharge.. We couldn't believe it "The team quickly realized the value of the visual protein authors say that although the channel is sensitive, normal ambient light does not cause the external cells in the animal to discharge it However, these animals should avoid bright light exposure Experiments mice showed that when the new visual protein (which the authors call "SOUL", meaning a step-function visual protein with ultra-high light sensitivity) is produced in cells anywhere in the brain, the blue light emitted by a fiber optic cable on the outside of the skull is enough to activate neurons In fact, the activation of SOUL neurons at about 5.5-6.2 mm on the outer side of the hypothalamus inhibits the eating behavior of hungry mice -- a known stimulus to this region to study the effectiveness of SOUL in the non-human primate brain, the team injected a virus that encodes the visual protein gene deep in the brain cortex of the macaque, reaching a depth of 5.6 mm The inserted multichannel probe shows that blue light activates neurons at all depths through a fiber optic cable placed on the outer membrane of the brain (through an opening on the skull) "This is a major advance in the study of the brains of non-human primates," albert Kamran Khodakhah, a neuroscientist at Einstein's Medical School, said he was not involved in the study However, he noticed some problems with brain oscillations observed by primates as a result of SOUL activation He said it was "very unexpected." "We don't know the exact cause of the oscillation," Feng said, "it's a potential mess" that needs further study He added, "Stimulating smaller brain regions or specific cell types may avoid this problem." Rafael Yuste, a neuroscientist at Columbia University , said this particular cell activation could be achieved by "using a double photon genetic with a single-cell resolution." Rafael Yuste was not involved in the work in addition to finding the source of the oscillation and ways to avoid it, Feng said, his team is now looking for ways to further improve the SOUL protein One possibility, he says, is to change the activation wavelength if SOUL is activated by red light, Corder says, "they may reach deeper depths." (BioValleyBioon.com) References: 1, Deep Brain Optogenetic Control With
OptogeneticS Creative Sion Sensory Without Input DBS with Nanoparticle-Based Optogenetics Modifies In Mice