Limitations of small-animal models

In the 1970s, scientists created the first wiring diagram of a worm brain. To do this, they sliced up a worm, imaged the slices under microscopes and then reconstructed a map of the worm’s neurons and their synaptic connections. Wonderful. (It was 302 neurons and really a map of the worm’s central nervous system.)

We haven’t come terribly far since then. It took until 2024 for scientists to create a full map – aka a connectome – of an adult fly brain (140,000 neurons) and researchers now dream of completing similar work for a mouse brain and one day perhaps a human brain with its 80 billion neurons and one trillion connections.

The belief is that if we have a proper wiring diagram of the brain, we will understand the brain and how it works much better.

Things have been slow and hard because mapping something like a mammalian brain requires a lot of laborious work, tons of computing power and some method for labeling all the neurons and their connections in a comprehensible and useful fashion.

E11 Bio was founded in 2021 to try and develop new techniques for mapping brains faster and cheaper. And today marks a big moment in the organization’s history. The E11 Bio team has published a paper – in conjunction with loads of high-profile contributors – detailing the success of its techniques. (There’s much more info on E11’s web site here and here.)

In very simplified terms, E11 can put viruses in the brain that carry proteins to neurons. Those proteins then distribute markers across the neurons that make them light up in different colors under a microscope. This technology has made it much easier to find individual neurons and trace their connections.

E11’s co-founder and CEO Andrew Payne was kind enough to come on the podcast to discuss the organization’s work and its brain mapping process. We also got into why this all matters, the challenges ahead and where neuroscience and artificial intelligence overlap.

Enjoy!

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