Jan 02, 2023 I Paul Seaburn

A Mouse With a Human Brain is Real and Responsive to Visual Stimuli

Most of us know someone whose actions and decisions make one wonder if they are operating with a mouse’s brain rather than a human one. Do mice ever find themselves in a similar situation – wondering if an odd-thinking rodent might be operating with the brain of an ant? What about the opposite – do mice look at an extremely smart mouse and wonder if they are somehow in possession of a human brain? That last one may actually be happening right now – engineers and neuroscientists have implanted human brain organoids or mini-brains in mice and those brains grew connections to the rodents’ cortex and responded to external sensory stimuli … in other words, the brains registered what the mice were seeing. Is this a good thing? Is it too late to ask?

How do I get one of these brains?

“But until now, no research team had been able to demonstrate that human brain organoids  implanted in the mouse cortex were able to share the same functional properties and react to stimuli in the same way. This is because the technologies used to record brain function are limited, and are generally unable to record activity that lasts just a few milliseconds.”

In a press release announcing their new paper, “Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex,” published in the journal Nature Communications, researchers from the University of California San Diego Department of Electrical and Computer Engineering explain how they overcame the challenges of determining what happens when a human brain organoid is implanted in the cerebral cortex of a mouse. Human brain or cortical organoids are mini brains grown from human pluripotent stem cells, which are usually derived from skin cells. They have proven to be useful tools for studying the effects of drugs on brain tissues to study the effects of drugs – particularly those used to treat neurodegenerative diseases. The ethics of creating brains that could develop a consciousness are generally addressed by destroying the mini-brains before that can happen, but researchers still run the risk of individual cells integrating with animal tissue and forming an animal-human hybrid. Ethicists derive some comfort from the fact that neither appears to have happened yet. This experiment may have changed that.

“No other study has been able to record optically and electrically at the same time.”

The UC San Diego-led team was comprised of both engineers and neuroscientists for a reason – the neuroscientists needed a new technology to detect millisecond microburst from mouse neurons. According to the press release, the team solved this problem by developing microelectrode arrays made from transparent graphene, and then using two-photon microscopic imaging on living tissue less than one millimeter in thickness. An array of electrodes was then placed on top of the human brain organoids transplanted inside a mouse cerebral cortex – the outer layer of neural tissue in human and animal brains. The results were astounding – the researchers were able to record neural activity electrically from both the implanted organoid and the surrounding host cortex in real time. They also saw mouse blood vessels growing into the human brain organoid – they eventually provided nutrients and oxygen to the mini-brain.

As astounding and revolutionary as that was, it was just the beginning.

“Researchers applied a visual stimulus–an optical white light LED–to the mice with implanted organoids, while the mice were under two-photon microscopy. They observed electrical activity in the electrode channels above the organoids showing that the organoids were reacting to the stimulus in the same way as surrounding tissue.”

In the next and most crucial phase of the experiment, the researchers exposed the mice with human mini brains to light and observed the stimulus get picked up first by the mouse’s own cerebral cortex and then passed to the implanted brain organoids area through functional connections. This new low noise transparent graphene electrode technology enabled the researchers to see spiking activity from the organoid and the surrounding mouse cortex ranging from high gamma oscillations and phase locking spikes to slow oscillations from mouse visual cortex.  According to the press release: “These findings suggest that the organoids had established synaptic connections with surrounding cortex tissue three weeks after implantation, and received functional input from the mouse brain.” However, the experiment did not end there.

“Researchers continued these chronic multimodal experiments for eleven weeks and showed functional and morphological integration of implanted human brain organoids with the host mice cortex.”

That’ right – the human mini brains continued to function in the mice cerebral cortexes for ELEVEN weeks … all the while interconnected with and growing blood vessels for food and oxygen. The study notes that the mice and the human mini brains were handled in compliance with all current guidelines by the government and scientific review boards. Is that really enough in this rapidly changing field where human brain tissue is functioning in a non-human mammal for eleven weeks? And that tissue is a brain which is responding to visual input through the rodent’s eyes as if it is the actual brain of the mouse? A 2018 symposium at Oxford University brought together experts in the field, philosophers and lawyers to debate these ethical concerns, and the Brainstorm project at Case Western University in Cleveland is monitoring labs working with brain organoids in an attempt to begin the “building of a philosophical framework” for future laws and guidelines. While those are in their early stages, it appears that joint technology/neuroscience experiments like this one at the University of California San Diego are barreling ahead at breakneck speeds to stay one step ahead of any new regulations and ethical restrictions. Of course, their defense is that these mini brains in mouse heads are for the good of those suffering from currently untreatable brain diseases and disorders. As the press release concludes:

“We envision that, further along the road, this combination of stem cells and neurorecording technologies will be used for modeling disease under physiological conditions; examining candidate treatments on patient-specific organoids; and evaluating organoids’ potential to restore specific lost, degenerated or damaged brain regions.”

Would a thinking mouse end these experiments?

How do you feel about human brains – even mini ones grown in a lab from stem cells grown from skin cells – being implanted in mice where they grow, connect to the cerebral cortex of the host and function for months? Are we the ones operating with the brain of a mouse?

With a nod to George Orwell … we are living in a new world – are we brave enough to deal with it?

Paul Seaburn

Paul Seaburn is the editor at Mysterious Universe and its most prolific writer. He’s written for TV shows such as "The Tonight Show", "Politically Incorrect" and an award-winning children’s program. He's been published in “The New York Times" and "Huffington Post” and has co-authored numerous collections of trivia, puzzles and humor. His “What in the World!” podcast is a fun look at the latest weird and paranormal news, strange sports stories and odd trivia. Paul likes to add a bit of humor to each MU post he crafts. After all, the mysterious doesn't always have to be serious.

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