Mini-brains attach to spinal cord and twitch muscles
A new method of growing mini-brains produces some startling results.
- Researchers find a new and inexpensive way to keep organoids growing for a year.
- Axons from the study's organoids attached themselves to embryonic mouse spinal cord cells.
- The mini-brains took control of muscles connected to the spinal cords.
Three things distinguish the lentil-sized mini-brains developed by Dr. Madeline Lancaster, of the Medical Research Council's Laboratory of Molecular Biology at Cambridge, and her colleagues.
First, a new method of supplying them nutrition has allowed the organoids to survive and continue developing for over a year. Second and third, they're the first organoids attached to spinal cords and muscle tissue, and — here's the startling part — they reached out and connected themselves to those spinal cord cells. Oh, also: They made the muscle tissue twitch.
Scientists such as Lancaster have been experimenting with organoids for a while now to improve our understanding of brain development and neurological disorders. However, her team's new research, just published in Nature Neuroscience on March 18, has, in light of these findings, taken things to another level.
How brainy is an organoid?
Before getting too creeped out, it's worth taking a moment to understand the rudimentary nature of organoids as they currently exist. The human brain is believed to contain some 100 billion neurons. The most advanced organoids so far possess just a couple of million — twice what a cockroach has and much less than an adult zebrafish. Still quite capable, but hardly human, it's becoming clearer that animals with fewer neurons than we have are likely sentient. The value of having organoids for research, however, is obvious, opening a window into all manner of human processes and diseases.
All that having been said, it can be expected that mini-brains will grow more and more sophisticated over time. This raises all sorts of ethical questions we should be addressing now, before we have a problem on our hands, if we don't already.
Happy ‘birthday,’ mini-brain
Most organoids don't grow for very long, because as the organoid grows, the nutrient solution in which it bathes can no longer reach its innermost neurons, and they die, terminating the growth cycle. In this research, scientists employed an "air-liquid interface culture." The primary purpose of the research was to verify the value of such an approach.
Each organoid was sliced into 1/2 millimeter-thick slices and attached to a membrane that was then introduced to a nutrient solution. This allowed the central neurons of each ALI-CO (for "air-liquid interface cerebral organoid") to continue receiving oxygen and nutrients. The organoids grew and produced new, healthy cells for more than one full year.
Because the ALI-COs' slice cultures were relatively easily to manipulate, the scientists were able to perform live imaging of them to assess their progress and the structures they developed. To identify the cells being produced, the team employed single-cell RNA (scRNA) sequencing to analyze six slices from three ALI-COs' cells, with an average of 4,427 cells per sample.
The live imaging revealed that axons, the nerve fibers that connect neurons, produced healthy outgrowths "reminiscent of nerve tracts" in the ALI-COs throughout the study, and various natural turning behaviors were observed. Neurons also successfully developed complex dendrites — connectors — as the organoids continued to grow. The complement of cells in the organoids was reminiscent of those in an organic embryonic brain.
Overall, the study found that that air-liquid interface culturation provides a viable, and less expensive, means of successfully growing healthy, fully-functional organoids for research purposes. The final proof of its efficacy was the spinal-cord connection.
Reach out and touch…something
As the final test of the ALI-COs' complexity, cells of spinal column attached to back muscle tissue from embryonic mice were co-cultured with the organoids.
"After 2–3 weeks in co-culture," reports the study, "dense axon tracts from the ALI-COs could be seen innervating the mouse spinal cord, and synapses were visible between human projecting axons and neurons of the mouse spinal cord." One might reasonably ask why: What did the "brain" have in "mind?" Let's hope it's simply instinctive behavior on a cellular level.
Next, the back muscles started twitching. While random muscle contraction occurs in disconnected tissue, these were much stronger, were arhythmic pulses, and could be switched off by severing the axonal connections. To further verify what seemed to be happening, researchers directly stimulated remaining axonal connections and verified their ability to produce muscle contractions. Also, the "evoked muscle contractions were intensity-dependent such that larger stimulation currents increased the amplitude of the muscle contraction." There's thus little doubt that the mini-brains were controlling the muscles connected to the spinal cords they'd reached out to and connected to. Welcome to the future.
To create wiser adults, add empathy to the school curriculum.
- Stories are at the heart of learning, writes Cleary Vaughan-Lee, Executive Director for the Global Oneness Project. They have always challenged us to think beyond ourselves, expanding our experience and revealing deep truths.
- Vaughan-Lee explains 6 ways that storytelling can foster empathy and deliver powerful learning experiences.
- Global Oneness Project is a free library of stories—containing short documentaries, photo essays, and essays—that each contain a companion lesson plan and learning activities for students so they can expand their experience of the world.
This is what the world will look like, 250 million years from now
To us humans, the shape and location of oceans and continents seems fixed. But that's only because our lives are so short.
The future of education and work will rely on teaching students deeper problem-solving skills.
- Asking kids 'What do you want to be when you grow up?' is a question that used to make sense, says Jaime Casap. But it not longer does; the nature of automation and artificial intelligence means future jobs are likely to shift and reform many times over.
- Instead, educators should foster a culture of problem solving. Ask children: What problem do you want to solve? And what talents or passions do you have that can be the avenues by which you solve it?
- "[T]he future of education starts on Monday and then Tuesday and then Wednesday and it's constant and consistent and it's always growing, always improving, and if we create that culture I think that would bring us a long way," Casap says.
These Jurassic predators resorted to cannibalism when hit with hard times, according to a deliciously rare discovery.
- Rare fossil evidence of dinosaur cannibalism among the Allosaurus has been discovered.
- Scientists analyzed dinosaur bones found in the Mygatt-Moore Quarry in western Colorado, paying special attention to bite marks that were present on 2,368 of the bones.
- It's likely that the predatory carnivore only ate their already-dead peers during times when resources were scarce.
As a doctor, I am reminded every day of the fragility of the human body, how closely mortality lurks just around the corner.