The idea of growing a functioning human brain-like tissue in a dish has always sounded pretty far-fetched. Towards this goal, researchers at the University of Tokyo have developed a technique for connecting lab-grown brain-mimicking tissue in a way that resembles circuits in our brain.
Formation and characterization of the connected organoids. Image credit: Osaki et al., doi: 10.1038/s41467-024-46787-7.
“It is challenging to study exact mechanisms of the brain development and functions,” said University of Tokyo’s Dr. Yoshiho Ikeuchi and colleagues.
“Animal studies are limited by differences between species in brain structure and function, and brain cells grown in the lab tend to lack the characteristic connections of cells in the human brain.”
“What’s more, we are increasingly realizing that these interregional connections, and the circuits that they create, are important for many of the brain functions that define us as humans.”
“Previous studies have tried to create brain circuits under laboratory conditions, which have been advancing the field.”
The authors found a way to create more physiological connections between lab-grown neural organoids, an experimental model tissue in which human stem cells are grown into three-dimensional developmental brain-mimicking structures.
They did this by linking the organoids via axonal bundles, which is similar to how regions are connected in the living human brain.
“In single-neural organoids grown under laboratory conditions, the cells start to display relatively simple electrical activity,” said University of Tokyo’s Dr. Tomoya Duenki.
“When we connected two neural organoids with axonal bundles, we were able to see how these bidirectional connections contributed to generating and synchronizing activity patterns between the organoids, showing some similarity to connections between two regions within the brain.”
The cerebral organoids that were connected with axonal bundles showed more complex activity than single organoids or those connected using previous techniques.
In addition, when the researchers stimulated the axonal bundles using a technique known as optogenetics, the organoid activity was altered accordingly and the organoids were affected by these changes for some time, in a process known as plasticity.
“These findings suggest that axonal bundle connections are important for developing complex networks,” Dr. Ikeuchi said.
“Notably, complex brain networks are responsible for many profound functions, such as language, attention, and emotion.”
“Given that alterations in brain networks have been associated with various neurological and psychiatric conditions, a better understanding of brain networks is important.”
“The ability to study lab-grown human neural circuits will improve our knowledge of how these networks form and change over time in different situations, and may lead to improved treatments for these conditions.”
The study is published in the journal Nature Communications.
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T. Osaki et al. 2024. Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons. Nat Commun 15, 2945; doi: 10.1038/s41467-024-46787-7