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Implanted Organoid Connects to Brain, Reacts to Visual Cues

Mature neuron

(National Institute of General Medical Sciences, NIH)

29 Dec. 2022. Engineers and neuroscientists developed a circuit that in lab mice connects implanted lab-grown brain tissue to the brain’s cognitive center and responds to visual stimuli. A team at University of California in San Diego, Boston University, and the Salk Institute in La Jolla, California describe the technology and findings in the 26 Dec. issue of Nature Communications.

Researchers led by engineering professors Duygu Kuzum at UC-San Diego and Anna Devor at Boston University are seeking ways to test brain organoids, three-dimensional collections of neurons or nerve cells grown in the lab, as diagnostic devices for neurological disorders. Up to now, organoids are developed and used mainly as models for organ tissue to test new drugs or medical devices, particularly as replacements for lab animals. In this case, the team aims to demonstrate added functions for organoids, when implanted in the brain.

Kuzum’s lab studies neuro-electronics, particularly interfaces linking brain and electronic signals, including nanoscale circuits for imaging and optogenetics, light-activated genetic responses in cells and tissue. Devor and colleagues investigate imaging of neuronal circuits in the brain, including measurements and recordings of brain activity, as well as neuronal networks derived from stem cells. In 2018, researchers from both labs demonstrated a micro-circuit made from transparent graphene to capture optogenetic signals in the brains of lab animals. Also in 2018, Science & Enterprise reported on the Kuzum lab’s work with graphene circuits for recording images of brain activity.

Organoids derived from adult stem cells

Graphene is a carbon material similar to graphite found in pencils, with a thickness of one atom and an hexagonal atomic pattern. The material has many desirable properties: very light, strong, chemically stable, and can conduct both heat and electricity. Graphene’s electrical conductivity is somewhat limited, however, requiring Kuzum’s team in 2018 to enhance the basic material with platinum nanoparticles to enable graphene circuits to capture images.

In their new paper, the San Diego/Boston team tested the combination of lab-grown organoid tissue working with a transparent graphene circuit implanted in the brain to capture images of neural activity. The organoids in this case are derived from human induced pluripotent stem cells, also known as adult stem cells, which the team transformed in the lab into human neurons, and subsequently grown into 3-D brain tissue. The researchers implanted the organoids and micro-scale graphene circuits into the retrosplenial cortex of adult lab mice, a part of the brain dealing with learning and navigation, but also close to the brain’s visual center.

The team found implanted human neurons in the organoid integrate and communicate with mouse neurons. Using a technique called two-photon imaging that illuminates and visualizes 3-D images of cells and tissue, the researchers demonstrate the capture of brain signals from the organoid with the graphene circuit. In addition, the circuit records electrophysical changes in brain activity responding to visual stimuli from LED light.

The researchers believe the organoid/graphene technology can evolve into a platform for studying brain development and disease, as well as future brain prosthetics. “This experimental set-up,” says Kuzum in a UC-San Diego statement, “opens up unprecedented opportunities for investigations of human neural network-level dysfunctions underlying developmental brain diseases.”

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