Spatial orientation mechanisms surprisingly similar to ours

Researchers are turning to zebrafish to uncover the secret of place cells, which play a crucial role in forming mental maps of space, social networks, and abstract relationships. So far, place cells have only been found in mammals and birds, leaving the question of how other species represent the external world largely unanswered. A team of researchers from the Max Planck Institute for Biological Cybernetics has now found the first convincing evidence of place cells in the brain of the tiny zebrafish larva.

When we explore an unfamiliar city, we use various cues—landmarks, a sense of how far we’re going in one direction, perhaps a river we can’t cross—to create an internal map of our surroundings. Deep in the brain, in a structure called the hippocampus, a set of place cells play a key role in building our internal maps of the outside world. These place cells fire when we’re at specific locations in space and can self-organize into a set of different mental maps.

It is already known that mammals, including humans, and even birds, have place cells. However, the existence of place cells in other species is controversial. A group of researchers from the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, led by Jennifer Li and Drew Robson, has found the first conclusive evidence for the existence of place cells in zebrafish.

The study is published in the journal Nature.

Whole-brain recording during natural behavior

The researchers recorded the brain activity of young zebrafish as they explored their environment. These fish are completely transparent at just a few days old, allowing their tiny brains, which contain only 100,000 cells, to be observed.

It is even possible to make individual active neurons light up using fluorescent calcium indicators, because all neuronal activity is associated with fluctuations in calcium ion concentration. A key earlier invention by Li and Robson was essential for observing brain activity during navigation: tracking microscopes that move with freely swimming fish.

Using this experimental model, the team analyzed the spatial information encoded in each neuron in the fish’s brain. They identified a population of about 1,000 place cells in each fish, most of which fire only when the animal is in a specific location, while a few respond to multiple areas. “Collectively, the place cell population encodes spatial information,” Li says. “From the firing patterns of the place cells, we were able to decode the location of each fish over time, with an error of just a few millimeters.”

Strikingly, most place cells are found in the telencephalon, an area of ​​the zebrafish forebrain whose precise function has been debated for decades. “The high concentration of place cells in the telencephalon potentially confirms the long-standing conjecture that this brain region is a functional analogue of the mammalian hippocampus, in miniature,” comments Drew Robson.

A flexible mechanism that integrates different inputs

However, Li and Robson needed further evidence to conclude that the cells they had identified were indeed analogous to mammalian place cells. The first feature to test was whether place cells rely on self-motion or external cues. In terms of human experience, a cue such as “I have been walking straight ahead at a brisk pace for about a minute” relies on self-motion, while “I can see the Eiffel Tower” is an external cue.

In a series of experiments, the researchers manipulated both sources of information: by removing the fish from their environment and replacing them, removing landmarks, or rotating the behavioral chamber. They found that the fish integrate both external cues and movement signals to create their internal maps, just as we do.

Not only do fish appear to refine their spatial representational map as they become familiar with an unfamiliar environment, but they can also adapt to change: they use the same neural circuits to remember a second environment. When they return to their original environment, they do not need to map it from scratch, but can partially retrieve the representational map they had previously created. Thus, the place cell population exhibits a flexible memory system, another characteristic of mammalian place cells.

An emerging model organism for a complex neural network

The study authors plan to use zebrafish as a new model organism to unravel the mysteries of place cells. In addition to their role in creating mental maps of space, these cells are also essential for forming maps of social networks and abstract relationships, as well as for memory and planning. Although mammalian place cells have been the subject of intensive research since their Nobel Prize-winning discovery more than 50 years ago, scientists still do not fully understand the neural networks that generate place cells or how they support such a wide range of mental functions.

The main challenge has been the complexity and size of mammalian place cell networks, which makes it extremely difficult to study the entire network simultaneously. In contrast, the larval brain of zebrafish is one of the smallest biological systems capable of generating place cells.

Robson concludes: “Using this new minimal model, future studies can potentially trace all the inputs to each place cell and create detailed models of how place cells acquire all their unique properties.”

Provided by the Max Planck Institute for Biological Cybernetics