A research team has for the first time shown that 800,000 brain cells living in a dish can perform goal-directed tasks – in this case the simple tennis-like computer game, Pong. The results of the study are published in the journal Neuron.

Now they are going to find out what happens when their DishBrain is affected by medicines and alcohol.

“We have shown we can interact with living biological neurons in such a way that compels them to modify their activity, leading to something that resembles intelligence,” says lead author.

While scientists have for some time been able to mount neurons on multi-electrode arrays and read their activity, this is the first time that cells have been stimulated in a structured and meaningful way.

“In the past, models of the brain have been developed according to how computer scientists think the brain might work,” the author says. “That is usually based on our current understanding of information technology, such as silicon computing.

“But in truth we don’t really understand how the brain works.”

By building a living model brain from basic structures in this way, scientists will be able to experiment using real brain function rather than flawed analogous models like a computer.

The team, for example, will next experiment to see what effect alcohol has when introduced to DishBrain.

“We’re trying to create a dose response curve with ethanol – basically get them ‘drunk’ and see if they play the game more poorly, just as when people drink,” says the author.

That potentially opens the door for completely new ways of understanding what is happening with the brain.

“This new capacity to teach cell cultures to perform a task in which they exhibit sentience – by controlling the paddle to return the ball via sensing – opens up new discovery possibilities which will have far-reaching consequences for technology, health, and society,” says another author.

“We know our brains have the evolutionary advantage of being tuned over hundreds of millions of years for survival. Now, it seems we have in our grasp where we can harness this incredibly powerful and cheap biological intelligence.”

The findings also raise the possibility of creating an alternative to animal testing when investigating how new drugs or gene therapies respond in these dynamic environments.

“We have also shown we can modify the stimulation based on how the cells change their behaviour and do that in a closed-loop in real time,” says the author.

To perform the experiment, the research team took mouse cells from embryonic brains as well as some human brain cells derived from stem cells and grew them on top of microelectrode arrays that could both stimulate them and read their activity.

Electrodes on the left or right of one array were fired to tell Dishbrain which side the ball was on, while distance from the paddle was indicated by the frequency of signals. Feedback from the electrodes taught DishBrain how to return the ball, by making the cells act as if they themselves were the paddle.

“We’ve never before been able to see how the cells act in a virtual environment,” says the author. “We managed to build a closed-loop environment that can read what’s happening in the cells, stimulate them with meaningful information and then change the cells in an interactive way so they can actually alter each other.”

“The beautiful and pioneering aspect of this work rests on equipping the neurons with sensations — the feedback — and crucially the ability to act on their world,” says a co-author.

“Remarkably, the cultures learned how to make their world more predictable by acting upon it. This is remarkable because you cannot teach this kind of self-organisation; simply because — unlike a pet — these mini brains have no sense of reward and punishment,” the co-author says.

“The translational potential of this work is truly exciting: it means we don’t have to worry about creating ‘digital twins’ to test therapeutic interventions. We now have, in principle, the ultimate biomimetic ‘sandbox’ in which to test the effects of drugs and genetic variants – a sandbox constituted by exactly the same computing (neuronal) elements found in your brain and mine.”

The author says one exciting finding was that DishBrain did not behave like silicon-based systems. “When we presented structured information to disembodied neurons, we saw they changed their activity in a way that is very consistent with them actually behaving as a dynamic system,” the author says.

“For example, the neurons’ ability to change and adapt their activity as a result of experience increases over time, consistent with what we see with the cells’ learning rate.”

https://www.cell.com/neuron/fulltext/S0896-6273(22)00806-6

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fin-vitro-neurons-learn&filter=22