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    Home > Active Ingredient News > Study of Nervous System > For the first time, human brain organoids were shown to establish functional connections and respond to external stimuli when implanted in mouse brains

    For the first time, human brain organoids were shown to establish functional connections and respond to external stimuli when implanted in mouse brains

    • Last Update: 2023-02-03
    • Source: Internet
    • Author: User
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    Written byNagashiEditor
    Wang Duoyu
    TypesettingThe wisdom of Shui Chengwen
    comes from the brain
    .
    Complex physiological phenomena such as memory, language and emotions all stem from a series of electrophysiological activities of the brain, which allows humans to recognize the world and make immediate judgments and reactions
    to everything in the outside world.

    There is no doubt that the brain is the most complex organ in the human body
    .
    But until now, human understanding of the behavior patterns of their own brains has been extremely limited
    .

    Recently, researchers at the University of California, San Diego published a title in the journal Nature Communications entitled Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual Cortex's research paper
    .

    The study is the first to demonstrate that human brain organoids implanted in mice establish functional connections to the mouse cerebral cortex and respond to
    external sensory stimuli.
    The implanted human brain organoids respond to visual stimuli in the same way as surrounding tissue, and the researchers were able to observe this in real time over several months, thanks to an innovative experimental setup
    that combines a transparent graphene microelectrode array and two-photon imaging.


    Human cortical organoids are derived from induced pluripotent stem cells (iPSCs), while induced pluripotent stem cells are typically derived from skin cells
    .
    These brain organoids have recently become promising models
    for studying human brain development as well as a range of neurological disorders.
    But so far, no research team has been able to demonstrate that human brain organoids implanted in the mouse cortex are able to share the same functional properties and respond
    to stimuli in the same way.

    This is because current technology for recording brain function is so limited that it is often impossible to record brain activity
    that lasts only a few milliseconds.
    Today, Professor Duygu Kuzum's team at the University of California, San Diego, has successfully solved this problem by developing a technique that combines microelectrode arrays made of transparent graphene with two-photon imaging,
    a microscopy technique that can image living tissue up to 1 millimeter thick.


    Professor Duygu Kuzum's team first developed transparent graphene electrodes in 2014 and have been advancing the technology
    ever since.
    The research team used platinum nanoparticles to reduce the impedance of the graphene electrode by a factor of 100 while maintaining its transparent properties, and the low-impedance graphene electrode was able to record and image neuronal activity
    at the macroscopic and single-cell level.

    By placing such an electrode array on the transplanted organoids, the research team was able to record real-time neural activity
    from the implanted organoids and the surrounding host cortex.
    Through two-photon imaging, they also observed mouse blood vessels growing into organoid implants, providing them with the necessary nutrients and oxygen
    .

    The generation of human cortical organoids and the co-implantation of microelectrode arrays in the mouse cortex Not only that, the research team also applied a white LED for visual stimulation to the mice implanted
    with organoids, while performing two-photon microscopy on the mice
    。 They observed electrical activity of electrode channels on organoids, suggesting that organoids respond to stimuli in the same
    way as surrounding host cortical tissue.
    Electrophysiological activity propagates
    through functional connections from the area of the implanted organoid area closest to the visual cortex.


    In addition, this transparent graphene electrode technology is able to record electrical spike signals in organoids and surrounding mouse cortex, and graphene recordings show an increase in the power of gamma oscillations, and spike phase locking
    of slow oscillations from organoids to the mouse visual cortex.
    The findings suggest that the organoids established synaptic connections with surrounding cortical tissue three weeks after implantation and received functional input
    from the mouse brain.

    The multiunit activity
    study team of human cortical organoids and host cortex continued this experiment for 11 weeks and showed the functional and morphological integration
    of implanted human cortical organoids with the cerebral cortex of host mice.
    The research team next plans to conduct more experiments involving neurological disease models, as well as incorporating calcium imaging in experimental settings to visualize peak activity
    in organoid neurons.
    These methods can also be used to track axon projections
    between organoids and the mouse cortex.

    Professor Duygu Kuzum said that in follow-up studies, the combination of stem cell and neural recording techniques will be used to model diseases under physiological conditions, examine candidate treatments for patient-specific organoids, and assess the potential
    of organoids to restore specific loss-of-function, degenerative or damaged brain regions.

    In vivo imaging and postmortem immunohistochemical analysis
    of human cortical organoid vascularizationIn summary, this study combines microelectrode arrays made of transparent graphene and two-photon imaging techniques.
    This enables recording and imaging of neuronal activity
    at the macroscopic and single-cell level.
    This technique shows that human cerebral cortical organoids generated by iPSCs can establish synaptic connections with surrounding host cortical tissues after implantation in mouse brains, and receive visual stimulation input from mouse brains to produce corresponding electrophysiological responses
    .

    This innovative neurorecording technology will create a unique platform for studying brain organoids, providing an unprecedented opportunity
    to study dysfunction at the level of human neural networks and to study the use of cerebral cortical organoids as neurofixes to restore function in function-loss-loss, degenerate, or impaired brain regions.

    Link to paper: style="color: rgb(136, 136, 136);font-size: 12px;" _mstmutation="1" _istranslated="1">
    Open reprint, welcome to forward to Moments and WeChat groups 
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