Here's a puzzle for you. Using the building blocks of a nervous system, design the perfect brain.

You have two types of cells to work with: neurons, and glia. Where would you put this agglomeration inside a body? For an animal to be considered relatively intelligent, they should have memory. Would your brain be solely focused on retaining and recalling events from the past, or should it also help the creature see and touch… maybe even move? You probably would design a brain unlike any other, but nature might have made one that’s even more bizarre. Cue the cephalopods.

Cephalopods are octopuses, squids, cuttlefish, and nautiluses. These animals are grouped together not only because they all possess many arms but also because they share an evolutionary tree branch with a common ancestor from around 500 million years ago. Their central brains form a ring around their esophagus and their arms are constantly testing the environment, processing the information they gather, thinking for themselves.

Despite their donut brain, some cephalopods are lauded for being the most intelligent invertebrates. Cuttlefish can count up to 5, on par with infant humans and young monkeys. Octopus are creative and use tools,  seen awkwardly carrying their home for protection. Hungry cuttlefish will resist mediocre treats for tastier ones delivered later, a sign of intelligence thought to be important for decision making and planning. While researchers have only recently started to systematically characterize the cognitive capabilities of these animals, decade old stories hint at an incredible mind.

In addition to a smart brain, some cephalopods have arms with little "brains" of their own. Invertebrate nervous systems often have dispersed clusters of neurons (called ganglia) in a line or aligned in pairs like a ladder. In cephalopods, some of these ganglia lumped together to form a central brain while some information processing capabilities stayed behind to control the arms. As the central brain is thought to direct generalized arm movements, nuanced movements are driven by the arm-specific nerve-bundles. Despite the arms sometimes described to have their own “brains,” these structures are too simple to produce what we might consider a consciousness. Regardless, the majority of the animals’ neurons reside in the arms and these arms can act on their own.

Since these arms have such incredible information processing capacities, a recent study asked whether individual cuttlefish arms can learn. The cuttlefish were presented with prey (a prawn) in a clear tube. The cuttlefishes initially lunged toward the prawn guided by their arms, but they would slowly decrease this behavior as they learned that the prawn is inaccessible.

The researchers then looked for molecular traces of memory formation by counting the number of cells in the arm containing a protein in a certain configuration. This protein, called CREB, can be found immediately after cells are active and is a popular protein to track in learning studies.

By looking at neurons in the arms, they found more CREB-expressing cells in cuttlefish that learned to stop attacking a tubed prawn than in cuttlefish who were not trained. These CREB expressing neurons clustered around the suckers which are involved in obtaining touch and taste information. Seeing CREB by the sensory apparatuses, the researchers wondered if all of the learning is occurring in the arms without input from the brain.

This is an interesting investigation raising a fascinating question regarding how much these limbs are capable of, but there are major caveats to this study. For example, does CREB really indicate that a memory formed here or does it just indicate the arm was recently touching something? And one is left to wonder how much influence the central brain has in this kind of learning or whether the arms truly learn on their own. While the implications are exciting, the findings here are still very preliminary.

Most intelligent animals have nervous systems resembling our own brain and a spinal cord. Meanwhile, some cephalopods have keen intelligence with a donut-shaped brain and a more dispersed nervous system. How did this happen?

Cephalopods and humans are distant evolutionary relatives sharing a common ancestor from about 600 million years ago. This makes us more related to insects than cephalopods and they are in turn more related to oysters and clams. Since the evolutionary split occurred in a common ancestor that had a rudimentary nervous system, we all have similar neurons. Humans and cephalopods use the same signals between neurons (neurotransmitters) and our neurons function similarly. The most notable differences between our nervous systems and theirs seem to be structural.

The striking differences in brain structure and the large evolutionary gap indicates intelligent brains evolving twice: once in vertebrates and separately in cephalopods. These brains are also thought to have evolved under different pressures with mammals and birds evolving to accommodate social environments while cephalopods needed to evade predators and creatively eat other sea creatures. With these differences, it’s interesting to note that some types of memory and learning are present in both groups of animals (like episodic memory, semantic memory, spatial memory, and social memory). Additionally, these clever animals all have specialized brain regions dedicated to processing information, rather than relaying sensory or motor signals. And it’s this structure that forms and retains long-term memories.

With such different evolutionary pressures, a brain that defies age related cognitive decline is also possible. Another recent study assessed episodic-like memory in cuttlefish and saw that old animals performed just as well as young ones (episodic memory relates to remembering specific past events). The researchers trained cuttlefish to recognize that a black and white stiff flag signals food. Two identical flags would be presented at once and then replaced with a mediocre or tasty treat. After the initial reveal, the animals had to remember where the flags were and which location corresponded to which treat for later snack retrievals. The location of these flags changed daily, so the cuttlefish also had to learn to remember which new location was associated with their preferred food. The food delivery also differed by food type, so they had to get the timing right too.

When cuttlefish were trained to remember when and what they were fed, the older cuttlefish did just as well as the young cuttlefish even though they showed other signs of aging. Most of the older cuttlefish even died naturally just days after the experiment (RIP). Episodic and episodic-like memory decline is seen in older humans, non-human primates, and rodents, so this finding in cuttlefish is quite impressive. In the other animals, memory decline is attributed to age related changes in a part of the brain called the hippocampus. Cuttlefish, however, don’t have a hippocampus so learning and memory are said to instead involve their vertical lobe.

Some researchers have wondered whether cognitive deterioration with time is only natural and unavoidable, but perhaps this isn’t the case. Maybe, just maybe cuttlefish hold the key to having a sharp mind indefinitely.