How big brains are made

Cephalopods are capable of some truly impressive behaviors. They can quickly process information to transform shape, color, and even texture, blending in with their surroundings. They can also communicate with one another, show signs of spatial learning, and use tools to solve problems. They are so smart they even get bored and start making mischief.

It’s no secret what makes this all possible: These marine animals, which include octopus, squid, and their cuttlefish cousins, have the most complex brains of any invertebrates on the planet. What remains something of a mystery, however, is how cephalopods developed those big brains in the first place. A Harvard lab that studies the visual systems of these soft-bodied creatures — which is where two-thirds of their central processing tissue are focused — believe they’ve come close to figuring it out.

Researchers from the FAS Center for Systems Biology describe in a new study how they used a new live-imaging technique to watch neurons being created in squid embryos almost in real-time. They were then able to track those cells through the development of the nervous system in the retina.

They were surprised to discover that these neural stem cells behaved very much like those in vertebrates during nervous-system development. The results suggest that while vertebrates and cephalopods diverged from one other 500 million years ago, the process by which both developed big brains was similar. In addition the way the cells act, divide, and are shaped may essentially follow a kind of blueprint required for this kind of nervous system.

“Our conclusions were surprising because a lot of what we know about nervous system development in vertebrates has long been thought to be special to that lineage,” said Kristen Koenig, a John Harvard Distinguished Fellow and senior author of the study. “By observing the fact that the process is very similar, what it suggested to us is that these two independently evolved, very large nervous systems are using the same mechanisms to build them. What that suggests is that those mechanisms — those tools — the animals use during development may be important for building big nervous systems.”

The scientists from the Koenig Lab focused on the retina of a squid called Doryteuthis pealeii, more simply a longfin inshore squid. The squid grow to be about a foot long and are abundant in the northwest Atlantic Ocean. The embryos look like adorable anime characters with big heads and eyes.

The researchers employed similar techniques to those regularly used to study model organisms, like fruit flies and zebrafish. They created special tools and made use of cutting-edge microscopes that can take high-resolution images every 10 minutes for hours on end to see how individual cells behave. The researchers used florescent dyes to mark the cells so they could map them and track them.

This live-imaging technique allowed the team to observe stem cells called neural progenitor cells and how they are organized. The cells formed a special kind of structure called a pseudostratified epithelium. Its main feature is that the cells are elongated so they can be densely packed. Researchers also saw the nucleus of these structures move up and down before and after dividing. This movement is important for keeping the tissue organized and allowing for continued growth, they said.

This type of structure is universally seen in brain and eye development in vertebrate species. It long has been considered one of the reasons the vertebrate nervous system could grow so large and complex. Scientists have observed examples of this type of neural epithelium in other animals, but the squid tissue was also strikingly similar to that of vertebrates in size, organization, and nucleus movement.

The research was led by Francesca R. Napoli and Christina M. Daly, research assistants in the Koenig Lab.

Next, the lab plans to look at how different cell types in cephalopod brains emerge. Koenig wants to determine whether they’re expressed at different times, how they decide to become one type of neuron versus another, and whether this action is similar across species.

“One of the big takeaways from this type of work is just how valuable it is to study the diversity of life,” Koenig said. “By studying this diversity, you can actually really come back to fundamental ideas about even our own development and our own biomedically relevant questions. You can really speak to those questions.”