Researchers at Yale University have successfully grown mini versions of two crucial pieces of human brain tissue in the lab, demonstrating how neuronal activity stays in balance — and why things sometimes go awry.

Recent advancements in stem cell technology have made it possible for scientists to grow neural tissues in a lab. These are complex, 3D structures that mimic the way brains behave in the early stages of embryonic development. Researchers have figured out how to stimulate stem cells to grow into different kinds of brain tissue; each little bundle of cells that mimics a brain region is called an organoid.

The scientists in this study, led by Yangfei Xiang and Yoshiaki Tanaka, grew two organoids, each representing different regions of the brain in its early stages of development. The results were published online Thursday in Cell Stem Cell. One organoid represented an area of the brain called the medial ganglionic eminence, which plays a brief but important role in embryonic neural development by producing inhibitory neurons — the sort that send the signal for brain cells to stop firing off. These interact with excitatory neurons and in ideal conditions the system exists in balance as a whole.

 Intestinal organoid grown from Lgr5+ stem cells. St Johnston D (2015) The Renaissance of Developmental Biology. PLoS Biol 13(5): e1002149. doi:10.1371/journal.pbio.1002149
This is an intestinal organoid grown from stem cells. 

The research team managed to fuse their medial ganglionic eminence with another organoid made of excitatory neurons. From there, they could watch at a microscopic level the growth of the inhibitory neurons through the tissue, doing their thing to prevent the system from getting too fired up.

This mini-brain model offers scientists a way to peer into the functioning of the developing brain, which isn’t possible for technical and ethical reasons on actual human embryos. The research offers insights into how things can go wrong in the developing brain when the balance of inhibitory and excitatory neurons gets out of whack. Too much excitation is implicated in schizophrenia, whereas too little is implicated in depression. Autism spectrum disorders have also been linked to an imbalance in this important neuronal relationship.

Because these organoids are simplified models made of living brain tissue, they could also teach us a great deal about the evolution of grey matter. By first understanding how basic neural structures interact with each other, we may be able to uncover how our impossibly complex minds got to be the wa they are — and how.


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