Zebrafish Brain Study Reveals Shared Rules Across Vertebrate Evolution

Fish, birds and mammals diverged from shared ancestors hundreds of millions of years ago, and their brains have followed distinct evolutionary routes.

Nevertheless, scientists have long observed that these brains appear to tackle the same challenge in surprisingly similar fashions.

“You can really see it’s almost like a continuum,” explains Emre Yaksi, a professor at the Kavli Institute for Systems Neuroscience in Trondheim.

The new research, led by first author Dr Anh-Tuan Trinh, investigated whether this pattern reveals a more fundamental organisational principle common to vertebrates.

In all vertebrate brains, signals from the various senses initially travel through separate routes, before being merged into a single representation.

For mammals, the thalamus serves as a key relay hub, sending visual, auditory and other sensory signals to separate brain areas before higher regions unite them into perception and thought.

Imaging the zebrafish brain

To examine this process, the team used young zebrafish measuring under 1 centimetre long. The fish were carefully held in transparent gel beneath a microscope, while fresh water passed over their mouths to allow them to breathe comfortably.

Once the fish had adjusted to this arrangement, the scientists began measuring activity throughout the entire forebrain. Performing the experiment meant managing a complicated array of equipment.

“You activate a whole bunch of switches,” Trinh says. “It reminds me of the cockpit of an aeroplane, or a spaceship. There are so many buttons everywhere.”

Experience gained over several years made the work more manageable. “It’s like playing the piano. At first, it’s very hard. Over time you get better,” Trinh continued.

The result was remarkable: rather than viewing a limited brain area, the team could follow real-time activity throughout the full forebrain.

“The first time I saw neurons lighting up here and there, it was just like fireworks in the brain. It was so amazing,” said Trinh.

Building a complete picture

The procedure was simple. Researchers presented the fish with flashes of red light, mild vibrations in the water around them, or both stimuli simultaneously. They then traced the path of each signal through the brain.

Their findings revealed that zebrafish receive sensory input through a brain structure different from the mammalian one. Rather than using the thalamus, they depend on an area known as the preglomerular complex, or PG.

While these structures are distinct, their roles are largely alike. The PG routes visual and vibration signals to different forebrain regions, maintaining their separation before later processing stages start to merge them.

The discovery indicates that evolution may have created different brain structures to carry out almost the same functions. Although the components differ, the broader organisation is notably similar.

Linking two senses

On examining the zebrafish forebrain more closely, the researchers uncovered an additional finding. Some neurons reacted solely to light, whereas others responded only to vibration.

Further into the brain, though, they identified neurons that reacted exclusively when the two signals occurred together.

These cells remained inactive in response to either stimulus by itself. When light and vibration were presented simultaneously, the neurons fired far more strongly than anticipated.

Building a bigger picture

Scientists think these neurons could enable the brain to identify that separate sensory signals form part of one event.

In daily life, people continually integrate information from several senses to make sense of their surroundings. The brain connects a lightning flash with thunder, although the two signals arrive at slightly different times.

Trinh found these distinctive neurons during data analysis after the experiment. “I was blown away. My first reaction was, is this real or not?”

Even after checking the findings repeatedly, the pattern persisted. “I literally spent ten minutes just looking at these beautiful plots.”

The team also identified a distinct hierarchy within the forebrain. More basic neurons processing individual senses were located nearer the back, whereas neurons combining information were increasingly common towards the front.

Researchers do not yet know precisely how these higher-level neurons affect behaviour, but they could help animals identify connections between events, a capacity that underpins learning and decision-making.

Beyond a fish brain

The results highlight a significant concept in neuroscience. The forebrain is not chiefly devoted to fundamental survival functions, such as moving or eating.

Instead, it helps animals react when their environment becomes uncertain and they must adjust to something unfamiliar.

Yaksi illustrated this idea with a cooking comparison. “You want to thicken your soup. You can put potatoes and rely on the starch, or you can put flour, and it also works. The solutions are similar, but you do not necessarily need to rely on the same material as long as it functions similarly.”

The researchers are now comparing zebrafish and mammalian brains at the molecular level, to establish whether these comparable circuits arose from related cell types or developed independently.

Rules across evolution

“I don’t argue that a fish has the equivalent of a mammalian cortex,” Yaksi says. “But a fish has something. It’s the pallium. And it evolved from the same vertebrate ancestors that our human cortices evolved from.”

Although much remains unknown about the fish forebrain, the researchers think they have located the point at which sensory information first enters this vital circuit.

“We just now learned where the world comes in. That is how everything starts.”

The study indicates that evolution repeatedly reaches a similar answer when constructing a brain capable of interpreting the world.

Fish and humans may rely on different brain structures, yet they seem to observe the same central principle: initially keep sensory information apart, integrate it progressively, and create a complete picture from numerous separate elements.

This common approach may be among the most ancient principles governing vertebrate brain organisation.

The complete study was published in the journal Science.