A zebrafish swims towards its intended target, but is blown off course by strong currents. However, the little fish swims back to its original location, determined to finish its journey.
How do animals know where they are in their environment and how does this determine their subsequent choices? Scientists at HHMI’s Janelia Research Campus discovered that the hindbrain, an evolutionarily conserved or “ancient” region at the back of the brain, helps animals calculate their location and use that information to figure out where to go. ‘go after
The new research, which is published in the journal Cell on December 22, uncovers new functions for parts of the “ancient brain,” findings that could apply to other vertebrates.
Whole-brain imaging reveals new networks
To find out how the animals understand their position in the environment, the researchers, led by En Yang, a postdoctoral fellow in the Ahrens Laboratory, placed a small translucent zebrafish, barely half a centimeter long, in an environment of virtual reality that simulates water currents. When the current changes unexpectedly, the fish initially drift off course; however, they are able to correct this movement and return to where they started.
As a zebrafish swims in the virtual reality environment, the researchers use a whole-brain imaging technique developed at Janelia to measure what is happening in the fish’s brain. This technique allows scientists to search the entire brain to see which circuits are activated during their course-correcting behavior and untangle the individual components involved.
The researchers expected to see activation in the forebrain, where the hippocampus is located, which contains a “cognitive map” of an animal’s environment. To their surprise, they saw activation in several regions of the medulla, where information about the animal’s location was relayed from a newly identified circuit through a hindbrain structure called the olive inferior to the cerebellar motor circuits that allow fish to move. When these pathways were blocked, the fish could not return to its original location.
These findings suggest that brainstem areas remember a zebrafish’s original location and generate an error signal based on its current and past locations. This information is transmitted to the cerebellum, allowing the fish to swim back to its starting point. This research reveals a new role for the inferior olive and cerebellum, which were known to be involved in actions such as reaching and locomotion, but not this type of navigation.
“We found that the fish tries to calculate the difference between its current location and its preferred location and uses that difference to generate an error signal,” says Yang, first author of the new study. “The brain sends this error signal to its motor control centers so that the fish can correct after being unintentionally moved by the flow, even many seconds later.”
A novel multiregional hindbrain circuit
It is not yet clear whether these same networks are involved in similar behavior in other animals. But the researchers hope that labs studying mammals will now begin to look for homologous circuits for navigation in the hindbrain.
This hindbrain network could also underlie other navigational skills, such as when a fish swims to a specific place for shelter, the researchers say.
“This is a very unknown circuit for this form of navigation that we believe may be the basis of higher-order hippocampal circuitry for landmark-based exploration and navigation,” says Janelia, leader of the senior group Misha Ahrens.
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