Octopuses reshape their own brains when they’re cold

Octopuses are some of the smartest animals on the planet, and some of the weirdest. They have roughly the same number of neurons as dogs, but more than half of those cells are spread across the glider’s eight arms rather than contained in a central brain.

As the researchers report on June 8 at Cell, the neural abnormalities only get weirder from there. Octopuses, they discovered, have the ability recode your neurons in response to temperature variations, these cells therefore produce different proteins. Like people who adapt their clothes to the weather outside, octopuses modify their RNA, which is a genetic molecule that carries the instructions from DNA to produce proteins, the workhorses of cells. Researchers suspect that these “brain changes” help octopuses adapt to heat or cold as the seasons change. And they do it “to an extraordinary extent,” says co-lead author Joshua Rosenthal, a biologist at the Marine Biological Laboratory in Woods Hole, Mass.

RNA editing occurs when an outside force activates certain enzymes inside the cells of the body which then make chemical changes to the RNA. Depending on the changes, cells produce different forms, or isoforms, of proteins. Since RNA is a transient molecule, any changes to the genetic information it carries will not be permanent, a characteristic that, in theory, makes it a powerful tool for instant acclimation to changing environmental conditions.

In humans, RNA editing affects protein production in less than 3% of genes, whereas Rosenthal and colleagues previously found that all sophisticated species of cephalopods—that is, all cephalopods other than nautiluses—can recode the majority of neuronal proteins.

The researchers wanted to follow up on this previous work to see what factors might drive RNA editing in cephalopods. They started with the change in temperature, because it is a simple environmental condition that fluctuates seasonally, even daily.

The scientists first collected a dozen California two-spotted octopuses (bimaculoid octopus), a species whose genome has already been sequenced. They acclimated the animals to tanks containing hot or cold water. Several weeks later, the researchers looked at around 60,000 previously identified sites in the animals’ genomes where enzymes modify RNA. They found that about a third of these sites had changed, and that those changes were happening quickly, on a scale of hours to days. “We expected to see a few sites here and there that had changed, but no, it was something very global,” says co-lead author Eli Eisenberg, a physicist at Tel Aviv University whose research focuses on on RNA.

Almost all of the changes were cold-induced, the team found. And among those changes were those that code for specific classes of proteins involved in cell membranes, the functions of synapses (which transmit neuronal signals), autophagy (programmed cell death) and calcium binding (which plays various roles within neurons). The researchers confirmed that the isoforms created via the modified RNA had altered functions, but “we don’t yet know how these thousands of changes, or some of them, promote adaptation,” says Eisenberg. “Understanding the overall effect of all concert changes is left for future studies.”

Finally, the team also collected wild octopuses, including another closely related species, Verrill’s two-spotted octopus (octopus bimaculatus)-summer, like winter. The researchers found that these individuals exhibited the same temperature-tracking RNA-related changes as the California two-spotted octopuses they tested in the lab.

Unlike humans and other mammals, octopuses cannot regulate their own temperature. The researchers therefore suspect that RNA editing plays a role in protecting invertebrate neurons against temperature fluctuations. “The organism chooses to express different isoforms, and each is best in its own state,” says Eisenberg. “There is not even a single example of this happening in mammals.”

Heather Hundley, a biologist at Indiana University in Bloomington, who was not involved in the research, calls the new paper “a real tour de force”.

“This work adds to the growing body of data demonstrating that RNA editing can be dynamically regulated,” she says. “While previous work has primarily focused on regulation during development and disease, this work demonstrates that RNA editing can serve as a molecular means to acclimate protein function in response to environmental changes in temperature. .”

Rosenthal, Eisenberg and their colleagues plan to continue this line of study by investigating additional factors that may trigger changes in protein production, such as pH and oxygen levels or the social environment. “How extensive is this ability to acclimate through RNA editing?” said Rosenthal. “There is a lot of interesting work to be done.”