Introducing the brain: human brain organoids in rat brains (Introduction)

by David Turell , Wednesday, October 12, 2022, 16:38 (562 days ago) @ David Turell

A great new ethical way to study human neuron networks:

https://www.quantamagazine.org/lab-grown-human-cells-form-working-circuits-in-rat-brain...

"Our understanding of the inner workings of the human brain has long been held back by the practical and ethical difficulty of observing human neurons develop, connect and interact. Today, in a new study published in Nature, neuroscientists at Stanford University led by Sergiu Paşca report that they have found a new way to study human neurons — by transplanting human brainlike tissue into rats that are just days old, when their brains have not yet fully formed. The researchers show that human neurons and other brain cells can grow and integrate themselves into the rat’s brain, becoming part of the functional neural circuitry that processes sensations and controls aspects of behaviors.

"Using this technique, scientists should be able to create new living models for a wide range of neurodevelopmental disorders, including at least some forms of autism spectrum disorder. The models would be just as practical for neuroscientific lab studies as current animal models are but would be better stand-ins for human disorders because they would consist of real human cells in functional neural circuits. They could be ideal targets for modern neuroscience tools that are too invasive to use in real human brains.

“'This approach is a step forward for the field and offers a new way to understand disorders of neuronal functioning,” said Madeline Lancaster, a neuroscientist at the MRC Laboratory of Molecular Biology in Cambridge, U.K., who was not involved in the work.

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"In the new work — which was also headed by Paşca’s Stanford colleagues Felicity Gore, Kevin Kelley and Omer Revah (now at the Hebrew University of Jerusalem) — the team inserted cortical human brain organoids into the somatosensory cortex of very young rat pups, before the pups’ brain circuitry was fully established. This gave the human neurons a chance to receive long-range connections from a key region that processes incoming sensory information. Then the researchers waited to see whether the organoid would grow in concert with the rest of the rat’s developing brain.

“'We discovered that if we put the organoid in at that early stage … it grows up to nine times larger than it initially was over a period of four or five months,” said Paşca. That translated to an area of humanlike brain tissue that covered about a third of one of the rat’s brain hemispheres.

"But even though the human neurons stayed together in the cortical area where they were surgically placed, the researchers demonstrated that they became active parts of the neural circuitry threaded deep within the rat’s brain. Most of the transplanted human neurons began responding to touch sensations from the rat’s whiskers: When puffs of air were directed at the whiskers, the human neurons became more electrically active.

"Even more surprising, the flow of neural signals could also run in the other direction and influence behavior. When the human neurons were stimulated with blue light (through a technique called optogenetics), it triggered a conditioned behavior in the rats that made them seek a reward by licking more often at a water bottle.

“'That means that we have actually integrated human cells into the circuitry,” said Paşca. “It’s not changing the circuits. … It’s just that human cells are now part of it.”

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"The transplanted cells didn’t perfectly mimic human brain tissue in their new setting. For example, they did not organize themselves into the same multilayered structure seen in the human cortex. (Nor did they follow the lead of surrounding rat neurons and form the barrel-like columns characteristic of the rat somatosensory cortex.) But the individual transplanted neurons did keep many of the normal human electrical and structural properties."

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"Paşca hopes that being able to study mature human neurons within rats will finally bring treatments for psychiatric disorders and neurological conditions closer. Others in the field are hopeful too. “If this organoid transplantation strategy can truly mimic disease signatures, this could really accelerate our path toward cures,” said Joel Blanchard, a neuroscientist at the Icahn School of Medicine at Mount Sinai.

Comment: this is a major advance. Functional human neurons helping rat brain ssignals but, as the article notes, not organized as if in a human brain. But the neurons can be studied.