Human Mini-brains in a Dish Are Generating Brain-like Activity

Brain organoids (aka mini-brains) — are 3D cellular models that represent aspects of the human brain in the laboratory. Brain organoids help researchers track human development, unravel the molecular events that lead to disease and test new treatments. They aren’t prefect replicas, of course. Brain organoids do not replicate cognitive function, but researchers can check how an organoid’s physical structure or gene expression changes over time or as a result of a virus or drug.

University of California San Diego researchers have now taken brain organoids one step further, achieving an unprecedented level of neural network activity — electrical impulses that can be recorded by multi-electrode arrays. Using data from babies born up to three-and-a-half months premature, the team developed an algorithm to predict their age based upon EEG patterns. The algorithm then read lab-grown brain organoids the same way, and assigned them an age.

The electrical impulse pattern for nine-month-old brain organoids revealed similar features to those of a premature infant who had reached full-term (40 weeks gestation).

Brain organoids went from producing 3,000 spikes per minute to 300,000 spikes per minute.

Muotri’s brain organoids can live for years in the lab, but their activity plateaus at nine months. He said a number of reasons might apply, including the lack of blood vessels or the need for additional neurons to continue maturing.

The better brain organoids can replicate the human brain in the lab, Muotri said, the less researchers will need to rely on animal models and fetal tissue to better understand and treat human disease.

Cell – Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development

• Long-term, single-cell transcriptomics reveals cortical organoid developmental dynamics
• Cortical organoids exhibit phase-amplitude coupling during network-synchronous events
• Differential role of glutamate and GABA in initiating and maintaining oscillations
• Network-level events are similar to the human preterm neonatal EEG features

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months. The spontaneous network formation displayed periodic and regular oscillatory events that were dependent on glutamatergic and GABAergic signaling. The oscillatory activity transitioned to more spatiotemporally irregular patterns, and synchronous network events resembled features similar to those observed in preterm human electroencephalography. These results show that the development of structured network activity in a human neocortex model may follow stable genetic programming. Our approach provides opportunities for investigating and manipulating the role of network activity in the developing human cortex.

SOURCES – Cell, University California and San Diego
Written By Alvin Wang,

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