What mechanisms do animals use to orient themselves in their surroundings and how does this influence their decisions and actions?

Whole-brain imaging reveals new networks that help zebrafish remember their last location.

A zebrafish swims in the direction of its planned destination, but powerful currents steer it off course. However, the small fish swims back to its starting point, determined to complete its adventure.

How do animals detect their location in their surroundings, and how does this influence their following choices? Scientists at the Janelia Research Campus of the Howard Hughes Medical Institute revealed that the hindbrain, an evolutionarily conserved or “ancient” part of the brain, helps animals calculate their position and utilize that knowledge to determine where they need to travel next.

The findings of the new study were published in the journal Cell today. The results may be applicable to other vertebrates.

Whole-brain imaging shows that there are new networks

In order to study how animals navigate their surroundings, a team of researchers led by En Yang conducted an experiment using small zebrafish placed in a simulated aquatic environment with changing currents. Despite being initially disoriented by the shifting currents, the fish were able to quickly correct their course and return to their starting point. This research was conducted in the Ahrens Lab, where Yang is a postdoctoral researcher.

Researchers use a whole-brain imaging method created at Janelia to see what is going on in a zebrafish’s brain as it swims in a virtual reality environment. Using this method, researchers may examine the whole brain to determine which circuits are engaged during the course-correcting activity and then isolate their respective roles.

Since the hippocampus stores a “cognitive map” of an animal’s surroundings, the researchers predicted that this area of the brain would become active. Surprisingly, scientists saw activity in numerous medulla areas, indicating that the cerebellum’s motor circuits, which allow fish to move, were receiving information about the animal’s position from a newly discovered circuit through a structure called the inferior olive in the hindbrain. When these paths were blocked, the fish couldn’t find its way back to where it started.

These results indicate that regions of the brainstem produce an error signal depending on the present and previous locations of a zebrafish and recall the zebrafish’s original position. The cerebellum receives this information, which enables the fish to swim back to its initial place. The inferior olive and cerebellum, previously thought to be engaged in reaching and movement, are now also implicated in this form of navigation, as discovered by this study.

“We found that the fish is trying to calculate the difference between its current location and its preferred location and uses this difference to generate an error signal,” adds first author Yang. “The brain sends that error signal to its motor control centers so the fish can correct after being moved by flow unintentionally, even many seconds later.”  

New multiregional hindbrain circuit

To what extent these same networks contribute to analogous behavior in other species is unknown. But the researchers expect that now that the hindbrain has been identified, mammalian research laboratories will start exploring similar pathways for navigation.

The researchers speculate that this hindbrain network may also serve as the foundation for other navigational abilities, such as when a fish swims to a certain location for protection.

“This is a very unknown circuit for this form of navigation that we think might underlie higher order hippocampal circuits for exploration and landmark-based navigation,” adds Janelia Senior Group Leader Misha Ahrens.

Source: 10.1016/j.cell.2022.11.022