Brain waves detected in mini-brains

A new method of stem cell culture has resulted in a network of neurons complex enough to produce electrical activity.

  • Sean Bailly

Section of a cerebral organoid. Each color corresponds to a different type of brain cell. [Muotri Lab / UCTV]

With some 86 billion neurons, the brain is a particularly difficult organ to study. One solution is to investigate a simplified system with fewer neurons. In 2013, Madeline Lancaster’s team from the Vienna Institute for Molecular Biotechnology created miniature brains, also known as brain organoids, from human stem cells in the laboratory.

Although these mini-brains are very useful to researchers, until now they have never observed electrical activity in them. Now they have. Alysson Muotri of the University of California, San Diego, and her team have improved organoid harvesting techniques and discovered that, after a period of development, brain waves similar to those seen in the brains of babies appear spontaneously premature

It was known that in the brains of these babies the electrical activity shows chaotic patterns. But what happened before, that is, how complex neural activity arises and develops, was completely unknown. Furthermore, although the work with rodents had made it possible to observe the activity of immature brains, the question arose as to whether this could be extrapolated to the human brain.

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Brain organoids offer an opportunity to study such questions. About the size of a pea, they are obtained from pluripotent human stem cells. If placed in an environment that reproduces the conditions in which the brain develops, these cells differentiate and form neurons that organize themselves in a three-dimensional structure. This results in a reduced and simplified version of the human cortex (brain region involved in the cognition and interpretation of sensory information). Building on previous work that had produced mini-brains without electrical activity, Muotri’s team refined the technique, allowing them to track hundreds of organoids for ten months.

The researchers first showed that organoids harbor the same cell types and proportions as human brains at the same stage of development. They also recorded the electrical activity of the organoids using multiple electrode arrays. Within a few months, the mini-brains produced activity never before seen in these systems. They were chaotic single-frequency electrical patterns, signals that are also detected in the immature brains of premature babies. Over time, the signals became more regular and more diverse in terms of frequency, a transition that indicates that mini-brains continue to develop as the number of neural connections increases.

Next, the authors created a deep learning program to study the formation of mini-brains. They used the brain wave recording of 39 babies born six to nine months after conception as a reference. By analyzing the signals from the organoids in different phases, the algorithm was able to predict the level of maturity of the minibrains. This confirms that human brains and organoids have comparable development. Therefore, the latter could be a model of great interest to study the development of the brain, but also diseases such as Alzheimer’s, epilepsy or autism, or to test drugs.

Despite this breakthrough, organoids remain rudimentary models and are a long way from representing the complexity of the human brain. The current work also raises ethical questions: from what moment can a miniature brain with brain activity be considered conscious? We still lack much knowledge about the brain to answer this thorny question.