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News Lost fish find their way, thanks to their

Video: This video demonstrates the virtual reality environment of a zebrafish larva. Fish traverse a 2D environment in the presence of simulated water currents.
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Image credit: Misha Arens

A zebrafish swims toward its intended target, but strong currents push it off course. Still, the little fish swam back to its original spot, determined to complete 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 have discovered that the hindbrain — an evolutionarily conserved or “old” region at the back of the brain — helps animals calculate their location and use that information to determine where they need to go next.

New research published in the journal cell December 22, New functions of parts of the “ancient brain” revealed, findings that could be applied to other vertebrates.

Whole-brain imaging reveals new network

To find out how animals understand their place in the environment, researchers led by En Yang, a postdoctoral fellow in Ahrens’ lab, placed tiny translucent zebrafish, less than half a centimeter long, in a virtual reality environment that simulated water flow. When the water current changes unexpectedly, the fish are initially pushed off course; however, they are able to correct that movement and return to where they started.

When zebrafish swim in a virtual reality environment, the researchers used a whole-brain imaging technique developed by Janelia to measure what happens in the fish’s brain. This technique allows scientists to search the entire brain to see which circuits are activated during their course corrective behaviors and unravel the individual components involved.

The researchers expected to see activation in the forebrain — home to the hippocampus, 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 being transmitted from a newly discovered circuit through a hindbrain structure called the inferior olive to a motor circuit in the cerebellum, thereby Enables the fish to move. When these channels are blocked, the fish cannot return to their original positions.

These findings suggest that brainstem regions remember the zebrafish’s original location and generate false signals based on its current and past locations. This information is relayed to the cerebellum, allowing the fish to swim back to the starting point. The study revealed a novel function of the inferior olive and cerebellum, which are known to be involved in actions such as reaching and locomotion, but not in this type of navigation.

“We found that the fish was trying to calculate the difference between its current position and its preferred position, and using that difference to generate an error signal,” said Yang, the first author of the new study. “The brain sends that error signal to its motor control center so the fish can be corrected after being inadvertently moved by the current, even after a few seconds.”

A novel multiregional hindbrain circuit

It is unclear whether these same networks are involved in similar behaviors in other animals. But the researchers hope that labs studying mammals will now start studying the hindbrain, looking for cognate circuits used for navigation.

This hindbrain network may also underlie other navigational skills, such as when fish swim to specific places to avoid, the researchers said.

“This is a very unknown circuit for this form of navigation, and we think it may underlie higher-order hippocampal circuits for exploration and landmark-based navigation,” said Misha Ahrens, senior group leader at Janelia.

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