Researchers are looking into zebrafish to discover the mysteries of place cells, which are essential for creating internal maps of our physical surroundings, social circles, and abstract concepts. Up until this point, place cells have only been documented in mammals and birds, leaving a gap in understanding how other species perceive the world around them. A research group from the Max Planck Institute for Biological Cybernetics has recently gathered the first strong evidence of place cells present in the brains of larval zebrafish.
Researchers are looking into zebrafish to uncover the mysteries of place cells, which are vital for constructing mental maps of our surroundings, social networks, and abstract concepts. So far, place cells have been identified only in mammals and birds, which raises questions about how other species internally depict their external environment. A team from the Max Planck Institute for Biological Cybernetics has uncovered convincing evidence of place cells in the brains of tiny larval zebrafish.
When we navigate an unknown city, we rely on various indicators—such as landmarks, the distance we’ve traveled, or maybe an uncrossable river—to form a mental map of the surroundings. Inside the brain, in a region known as the hippocampus, a collection of place cells is vital for creating these internal maps. These cells activate when we find ourselves at particular locations, allowing them to create diverse mental representations of space.
This phenomenon has been well established in mammals, including humans, and even in birds. However, the presence of place cells in other kinds of species remains debated. A research team at the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, led by Jennifer Li and Drew Robson, has discovered the first solid evidence of place cells in zebrafish.
Recording the entire brain during natural behavior
The researchers monitored the brain activity of young zebrafish as they explored their surroundings. When they are just a few days old, these fish are fully transparent, which allows researchers to observe their tiny brains, containing a mere 100,000 cells. It’s even possible to illuminate individual active neurons using fluorescent calcium indicators, as neuronal activity leads to changes in calcium ion concentrations. A pivotal prior invention by Li and Robson facilitated the observation of brain activity during navigation: tracking microscopes that move along with the mobile fish.
Using this innovative approach, the team examined how spatial information is represented by each neuron in the fish’s brain. They identified a group of roughly 1,000 place cells in each fish, with most activating only when the fish was in a specific spot, while a few reacted to multiple locations. “Together, the place cell group encodes spatial information,” stated Jennifer Li. “From the firing patterns of the place cells, we were able to pinpoint each fish’s location over time—with an accuracy of just a few millimeters.”
Interestingly, most place cells were found in the telencephalon, a part of the zebrafish’s forebrain, which has sparked discussions about its specific role for decades. “The high density of place cells in the telencephalon potentially validates the long-held theory that this region acts as a smaller version of the mammalian hippocampus,” remarked Drew Robson.
A flexible mechanism that integrates different inputs
Nevertheless, Li and Robson needed more evidence to confirm that the cells they identified were truly analogous to mammalian place cells. The first feature they examined was whether these place cells rely on self-motion or external cues. For humans, a self-motion cue might be, “I’ve been walking straight for about a minute,” while an external cue could be, “I can see the Eiffel Tower.” In a series of experiments, the researchers altered both types of information—removing the fish from their environment, eliminating landmarks, or changing the orientation of the testing chamber. They discovered that the fish combine both external cues and self-motion cues to build their internal maps—similar to how humans do.
Not only do the fish refine their spatial mapping as they gain familiarity with a new environment, but they can also adjust to changes: they utilize the same neuronal pathways to remember a second location. When returned to their original setting, they don’t need to start mapping it again from scratch; instead, they can partially reconstruct the internal map they had previously developed. Thus, the collection of place cells demonstrates a flexible memory system, which is another characteristic of mammalian place cells.
An emerging model organism for a complex neuronal network
The researchers involved in the study aim to use zebrafish as a new model organism to delve deeper into the mysteries surrounding place cells. Beyond aiding in forming mental maps of physical space, these cells also play vital roles in mapping social connections and abstract relationships, along with being integral to memory and planning processes. Although the exploration of mammalian place cells has been extensive—especially following their Nobel Prize-winning discovery over five decades ago—the intricate neural networks that create place cells and their vast array of mental functions still remain partially understood.
The main obstacle has been the immense complexity and size of the networks in mammals, making a comprehensive study of all components very challenging. In contrast, the larval zebrafish brain represents one of the smallest biological systems capable of forming place cells. Robson concludes, “With this new minimal model, future research could potentially trace all inputs to each place cell and develop intricate models of how these cells acquire their unique characteristics.”
