Human brain organelles implanted in mouse cerebral cortex respond to visual stimuli for the first time
A group of engineers and neuroscientists showed for the first time that human brain organelles implanted in mice established a functional connection with the animal’s cerebral cortex and responded to external sensory stimuli.
The transplanted organelles responded to visual stimuli in the same way as the surrounding tissues. The scientists were able to conduct this observation in real time over several months thanks to an innovative experimental setup that combines graphene microchips with two-photon imaging.
The team, led by Duigo Kuzum, a faculty member in the Department of Electrical and Computer Engineering at the University of California, San Francisco, reveals the details of their findings in the Dec. 26 issue of Nature Communications.
Kuzum’s team collaborated with researchers from Anna Devor’s lab at Boston University, Alison R. Matri’s lab at UC San Diego, and Fred H. Gage’s lab at the Salk Institute.
The organelles of the human cerebral cortex are derived from pluripotent stem cells, which are usually derived from skin cells. That is, organelles are artificially grown clusters of cells that resemble the desired organ.
These brain organelles have recently emerged as promising models for studying the development of the human brain as well as a number of neurological conditions.
But so far, no research group has been able to prove that human brain organelles implanted in the cerebral cortex of mice have the same functional properties and respond to stimuli in the same way.
This is because the methods used to record brain functions are limited and generally cannot record activity that lasts only a few milliseconds.
The team was able to solve this problem by designing experiments that combine tiny arrays of transparent graphene electrodes with two-photon imaging, a microscopy technique that can image living tissue up to a millimeter thick.
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“No other study has been able to capture both visual and electrical information at the same time,” says Madison Wilson, first author of the paper and a doctoral student in the Kusum research group at the University of California, San Diego. “Our experiments show that visual stimuli elicit electrophysiological responses in organelles, identical to the electrophysiological reactions of the surrounding cortex.
“Multimodal monitoring of human cortical organs implanted in mice reveals a functional link to the visual cortex” Duygu Kuzum et al. Connection with nature https://t.co/NdqNDpiD3h
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The team hopes that this combination of innovative neural recording techniques for studying organelles will serve as a unique platform to comprehensively assess organelles as models of brain development and disease, as well as to explore their use as prostheses to restore function to lost, worn out, or damaged areas of the brain. .
“This experimental setup opens up unprecedented opportunities to investigate dysfunctions at the level of the human neural network that underlie developmental brain diseases,” said Kuzum.
By placing an array of these electrodes on the implanted organelle, the researchers were able to electrically record neural activity from both the implant and the host’s surrounding cortex in real time.
Using two-photon imaging, they also noticed that the mouse’s blood vessels had evolved into an organ that provided the transplanted body with essential nutrients and oxygen.
During the experiments, the team observed electrical activity in the electrode channels above the organelles, indicating that the organelles responded to the stimulus in the same way as the surrounding tissues.
Electrical activity propagates from the area closest to the visual cortex to the area of implanted organelles through functional connections.
The results show that the organelles established synaptic connections with the surrounding cortical tissue three weeks after transplantation and received functional signals from the mouse brain. The researchers continued these chronic multimodal experiments for eleven weeks and demonstrated the functional and morphological integration of human brain organs transplanted with the cerebral cortex of host mice.
The next steps include longer experiments with neuronal disease models, as well as incorporating calcium imaging into the experimental setup to visualize peak activity in neuronal organelles.
Source: Medical Express