Much of the earliest stages of development of the cerebral cortex remain unknown to scientists. What they do know is a great battle takes place between neurons that excite brain activity or inhibit it, essentially preventing overstimulation.
Until recently, it wasn’t possible to watch in real-time this process because it begins in a fetus during the second trimester of pregnancy. But for several years scientists at Stanford University's School of Medicine have been working to mimic in a petri dish critical features of development of a human cerebral cortex — essentially working to build models for watching a brain grow.
In their latest study, a team led by Sergiu Pasca, an assistant professor of psychiatry and behavioral sciences at Stanford, modeled 3D neural spheroids that were three to four millimeters in size, to study the normal development of the human forebrain.
The process lets neuroscientists monitor how brain development might go awry, said Pasca.
“The cerebral cortex is this beautiful balance of excitation and inhibition, of what’s essentially the yin and yang of the cortex,” Pasca said. “If you ruin this balance in the cortex and there’s too much excitation and too little inhibition, it can lead to seizures and epilepsy. Moreover, imbalances in this process are thought to lead to other psychiatric disorders, such as autism.”
The results were published in the journal Nature.
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Recapitulating features of the cerebral cortex in a dish opens up a window to explore the impact of drugs that, if added at the right time and at the right concentration, could potentially restore normal brain development.
Pasca said that 3D brain models have many advantages over mice models when studying brain development.
“Certain aspects of the human brain development may never be captured by a rodent model,” he said, explaining that development in mice might occur in just weeks, while in humans it spans many months, even after birth.
“We plan to use the platform to study a number of disorders, such as autism, epilepsy, schizophrenia, or bipolar disorder,” Pasca said. “This platform, by allowing us to assemble brain regions in vitro, could give us a window into various disorders associated with brain development.”
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