NBE Hong Guosong/Pu Kanyi Collaborate to Regulate Neural Activity Using Near-Infrared Light Penetrating the Brain

Editor-in-Chief | Xi The 2021 Nobel Prize in Physiology or Medicine was awarded to Professors David Julius and Ardem Patapoutian for their outstanding contributions to revealing the mechanism of human temperature and touch perception
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Julius discovered that behind the secret of human temperature perception is a group of membrane proteins called transient receptor potential (TRP family) ion channels
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These membrane proteins respond to different ranges of temperature, and one of the ion channels, called TRPV1, was the first TRP family to be discovered to be sensitive to heat
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More interestingly, Julius later discovered that rattlesnakes can sense the thermal effects of infrared radiation through TRP channel proteins in their buccal fossa for thermal imaging purposes
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On March 21, 2022, the research group of Hong Guosong of Stanford University and the research group of Pu Kanxi of Nanyang Technological University, Singapore jointly published the article Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field in Nature Biomedical Engineering illumination in the near-infrared-II window
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 Inspired by the above findings, the researchers proposed a novel idea: Can we learn from the thermal imaging mechanism of rattlesnakes in nature and use TRPV1 to make neurons in mammalian brains respond to near-infrared light? Compared with visible light used in traditional optogenetics, near-infrared light penetrates deeper in strong scattering media such as biological tissue, and is therefore more suitable as an energy transfer medium in non-invasive neuromodulation techniques
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However, the researchers encountered some difficulties in realizing this vision
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"Even near-infrared light, which penetrates deeply, is gradually scattered and absorbed in the brain
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These absorbed parts are then converted into heat
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Therefore, it takes a strong These high-intensity infrared light can cause much higher temperatures in the superficial brain regions than in the deep brain, thereby changing the behavior of neurons and even causing irreversible thermal damage
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" The first author of the article, fourth grader at Stanford University Doctoral student Wu Xiang described the difficulties they encountered earlier
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To solve this problem, researchers from the two groups designed a nanoconductor called MINDS (macromolecular infrared nanotransducers for deep-brain stimulation)
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MINDS efficiently converts near-infrared light to heat, making deep-brain neurons expressing TRPV1 more sensitive to near-infrared light
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In the experiment, MINDS located 5 mm deep in the brain produced higher localized warming than the shallower brain regions when illuminated by infrared light across the scalp
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The superior photothermal properties of MINDS can locally sensitize the response of neurons to infrared light, thereby enabling infrared neuromodulation within a safe radiation range
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 In order to demonstrate that MINDS and TRPV1 can safely use infrared light for effective neuromodulation in the deep brain, the researchers selectively expressed the TRPV1 channel protein in dopamine neurons located in the ventral tegmental area of ​​the mouse midbrain, and tried using infrared light to selectively express the TRPV1 channel protein.
Light excites these neurons to regulate the brain's reward circuitry
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In the conditioned place preference experiment, the researchers used different black and white stripes to mark the inner walls of the three arms of the Y-maze, and irradiated infrared light only at the end of one arm
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After three consecutive days of training with IR light, mice tended to stay within the IR lighted end, whereas controls lacking TRPV1 or MINDS showed no such place preference
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The recently reported near-infrared neuromodulation technique has many advantages over traditional electrical or optogenetic neurostimulation methods
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First, near-infrared light penetrates deeper into tissue than the visible light used in traditional optogenetics, thus avoiding tissue damage caused by permanent implantation of electrodes or fibers
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Second, the superior photothermal properties of MINDS allow us to use infrared light in the safe radiation range as a medium for neuromodulation
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In addition, infrared light can propagate almost non-destructively in the air, thus allowing researchers to place the light source at almost any distance above the subject's head, thereby eliminating the physical constraints of traditional methods on the subject's head
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In conclusion, the near-infrared neuromodulation technique reported in this article can penetrate the intact scalp and skull to excite neurons located in the deep brain
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As an extension of traditional optogenetics, this technique provides the possibility for neuromodulation in multi-subject social interaction behavioral experiments
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 Link to the original text: https://doi.
org/10.
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