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▎WuXi AppTec's content team edited the brain and is recognized as the most complex and mysterious human organ
.
To understand the mysteries of the human brain, such as how it develops and why it "malfunctions" — a range of neurological disorders that have required neuroscientists to rely on animal brains
for years.
In recent years, with technological breakthroughs in the field of stem cells, human brain organoids have provided a new model
closer to the human brain.
Recently, scientists have used innovative neural recording technology to confirm for the first time that human brain organoids implanted in mice can form functional connections with the original cerebral cortex of animals and respond
to external light stimuli.
▲The results of the study published in Nature Communications human brain
organoids use human induced pluripotent stem cells to differentiate, using specific culture conditions, these cells aggregate in a petri dish and self-assemble into three-dimensional tissues.
It is similar to the real human brain in terms of structure, cell type and other characteristics, and has complex neuroelectrical activity, just like a miniature human brain
.
In addition to these similarities, can human brain organoids also mimic the real brain in terms of functional properties? To this end, the scientists tried to implant the human brain organoids generated in the petri dish into the cerebral cortex of mice, monitor their neural activity in real time for a long time, and compare
the neural electrical activity of the organoid implant with the surrounding host cortex.
▲Microelectrodes made of transparent graphene record the electrical activity of organoids (Image source: Reference [2]; Credit: David Baillot/UC San Diego)
successfully achieved this without technological innovation
.
In this study, neuroscientists and engineers at the University of California, San Diego, developed a new technique that utilizes a low-impedance microelectrode array made of transparent graphene to record the electrical activity of neurons within brain tissue at the single-cell level
.
By placing the electrode array above the implanted organoids, the researchers could simultaneously record neural activity
from the implant and surrounding brain tissue.
At the same time, they used two-photon imaging technology for optical recording
.
It can be observed that the implanted organoids have mouse blood vessels, meaning that these implants can get oxygen
for the necessary nutrients.
▲ Human brain organoids and microelectrodes were implanted into the brains of mice for recording (Image source: Reference [1])
When the researchers applied visual stimulation to mice with white light, they found that according to the neuroelectrical activity recorded by the electrodes, Human brain organoids share the same electrical activity patterns as the
rat brain tissue around them.
Through functional connectivity, electrophysiological activity begins to propagate
from the region closest to the mouse visual cortex of organoid implants.
"Our experiments show that visual stimuli evoke electrophysiological responses in organoids that match
those in the surrounding cortex.
" Madison Wilson, the paper's first author and a postdoc, said
.
Not only the electrophysiological monitoring results showed that functional integration was formed between organoids implanted in mouse brains and host brains, but also immunostaining of brain tissues further proved that synaptic connections
were established between human-mouse neurons after organoid implantation.
Based on these findings, the team notes that the human brain organoids implanted in mice with transparent microelectrodes could serve many research purposes in the future, developing into a multifunctional in vivo platform for comprehensively assessing the development, maturation and functional integration of human neuronal networks, simulating disease, and assessing the potential of using organoids to repair damaged brain regions, among others
.
References: [1] Madison N.
Wilson et al.
, (2022) Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex.
Nature Communications Doi: https://doi.
org/10.
1038/s41467-022-35536-3 [2] Human brain organoids implanted into mouse cortex respond to visual stimuli for first time.
Retrieved Jan.
3, 2023 from style="margin-bottom: 0px;white-space: normal;text-align: center;line-height: 1.
75em;">
.
To understand the mysteries of the human brain, such as how it develops and why it "malfunctions" — a range of neurological disorders that have required neuroscientists to rely on animal brains
for years.
In recent years, with technological breakthroughs in the field of stem cells, human brain organoids have provided a new model
closer to the human brain.
Recently, scientists have used innovative neural recording technology to confirm for the first time that human brain organoids implanted in mice can form functional connections with the original cerebral cortex of animals and respond
to external light stimuli.
▲The results of the study published in Nature Communications human brain
organoids use human induced pluripotent stem cells to differentiate, using specific culture conditions, these cells aggregate in a petri dish and self-assemble into three-dimensional tissues.
It is similar to the real human brain in terms of structure, cell type and other characteristics, and has complex neuroelectrical activity, just like a miniature human brain
.
In addition to these similarities, can human brain organoids also mimic the real brain in terms of functional properties? To this end, the scientists tried to implant the human brain organoids generated in the petri dish into the cerebral cortex of mice, monitor their neural activity in real time for a long time, and compare
the neural electrical activity of the organoid implant with the surrounding host cortex.
▲Microelectrodes made of transparent graphene record the electrical activity of organoids (Image source: Reference [2]; Credit: David Baillot/UC San Diego)
successfully achieved this without technological innovation
.
In this study, neuroscientists and engineers at the University of California, San Diego, developed a new technique that utilizes a low-impedance microelectrode array made of transparent graphene to record the electrical activity of neurons within brain tissue at the single-cell level
.
By placing the electrode array above the implanted organoids, the researchers could simultaneously record neural activity
from the implant and surrounding brain tissue.
At the same time, they used two-photon imaging technology for optical recording
.
It can be observed that the implanted organoids have mouse blood vessels, meaning that these implants can get oxygen
for the necessary nutrients.
▲ Human brain organoids and microelectrodes were implanted into the brains of mice for recording (Image source: Reference [1])
When the researchers applied visual stimulation to mice with white light, they found that according to the neuroelectrical activity recorded by the electrodes, Human brain organoids share the same electrical activity patterns as the
rat brain tissue around them.
Through functional connectivity, electrophysiological activity begins to propagate
from the region closest to the mouse visual cortex of organoid implants.
"Our experiments show that visual stimuli evoke electrophysiological responses in organoids that match
those in the surrounding cortex.
" Madison Wilson, the paper's first author and a postdoc, said
.
Not only the electrophysiological monitoring results showed that functional integration was formed between organoids implanted in mouse brains and host brains, but also immunostaining of brain tissues further proved that synaptic connections
were established between human-mouse neurons after organoid implantation.
Based on these findings, the team notes that the human brain organoids implanted in mice with transparent microelectrodes could serve many research purposes in the future, developing into a multifunctional in vivo platform for comprehensively assessing the development, maturation and functional integration of human neuronal networks, simulating disease, and assessing the potential of using organoids to repair damaged brain regions, among others
.
References: [1] Madison N.
Wilson et al.
, (2022) Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex.
Nature Communications Doi: https://doi.
org/10.
1038/s41467-022-35536-3 [2] Human brain organoids implanted into mouse cortex respond to visual stimuli for first time.
Retrieved Jan.
3, 2023 from style="margin-bottom: 0px;white-space: normal;text-align: center;line-height: 1.
75em;">