How squids and octopuses get their big brains

Cephalopods—which include octopus, squid, and their cousins ​​cuttlefish—are capable of some truly charismatic behaviors. They can quickly process information to transform shape, color and even texture, harmonizing with their surroundings. They can also communicate, show signs of spatial learning and use tools to solve problems. They are so smart that they can even get bored.

It’s no secret what makes this possible: Cephalopods have the most complex brains of any invertebrate on the planet. What remains a mystery, however, is the development process. Basically, scientists have long wondered how cephalopods get their big brains in the first place. A Harvard lab studying the visual system of these soft-bodied creatures—where two-thirds of their central processing tissue is focused—believes they’ve come close to figuring it out. The process, they say, seems surprisingly familiar.

In a study published in Current Biology, researchers from the FAS Center for Systems Biology describe how they used a new live imaging technique to track the generation of neurons in the embryo in near real time. They were then able to follow these cells through the development of the nervous system in the retina. What they saw surprised them.

The neural stem cells they observed behaved in a strange way similar to the way these cells behave in vertebrates during the development of their nervous systems. It suggests that vertebrates and cephalopods, despite diverging from each other 500 million years ago, not only use similar mechanisms to build their large brains, but that this process and the way cells act , divided and shaped can essentially determine the the plan required development of this kind of nervous system.

“Our findings were surprising because much of what we know about nervous system development in vertebrates has long been thought to be specific to this lineage,” said Kristen Koenig, a John Harvard Distinguished Fellow and senior author of the study.

“Noticing the fact that the process is very similar, what it suggested to us is that these two independently evolved very large neural systems use the same mechanisms to build them. What it suggests is that these mechanisms – these tools – use the animals during development may be important for building large nervous systems.”

Scientists from the Koenig lab focused on the retina of a squid called Doryteuthis pealeii, more simply known as a type of long-winged squid. Squids grow to about a foot in length and are abundant in the northwest Atlantic Ocean. As fetuses, they look adorable, with big heads and big eyes.

The researchers used similar techniques to those that have become popular for studying model organisms such as fruit flies and zebrafish. They created special tools and used state-of-the-art microscopes that could take high-resolution images every ten minutes for hours to see how individual cells behaved. The researchers used fluorescent dyes to mark the cells so they could be mapped and tracked.

This live imaging technique allowed the team to observe stem cells called neural progenitor cells and how they are organized. The cells form a special type of structure called a pseudostratified epithelium. Its main characteristic is that the cells are elongated so that they can be densely packed. The researchers also saw the core of these structures move up and down before and after the division. This move is important to keep the web organized and continue to grow, they said.

This type of structure is universal in how vertebrates develop their brains and eyes. Historically, it was thought to be one of the reasons why vertebrate nervous systems could become so large and complex. Scientists have seen examples of this type of neural epithelium in other animals, but the squid tissue they examined in this case was unusually similar to vertebrate tissues in size, organization, and the way the nucleus moved.

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

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

Koenig is excited about the potential discoveries that lie ahead.

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