The hindbrain is the area of the brain that controls basic vital functions such as heart rate, breathing and balance. The hindbrain is considered the most primitive part of the brain and is the main link between the spinal cord and higher brain regions.
Multiregional hindbrain circuits enable animals to regain their paths after straying from them.
A zebrafish is headed toward its goal, but strong currents push it off course. Not discouraged, the little fish returned to the starting point, determined to complete its journey.
How do animals know where they are in their environment, and how does this determine their subsequent choices? Researchers at the Howard Hughes Medical Institute’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.
The new study, recently published in the journal cellrevealing new functions in parts of the “ancient brain,” findings that could be applied to other[{” attribute=””>vertebrates.
This video shows whole-brain recordings of the larval zebrafish taken while it was in the virtual reality environment. Credit: Misha Ahrens
Whole-brain imaging reveals new networks
To figure out how animals understand their position in the environment, researchers, led by En Yang, a postdoc in the Ahrens Lab, put tiny translucent zebrafish, barely half a centimeter in length, in a virtual reality environment that simulates water currents. When the current shifts unexpectedly, the fish are initially pushed off course; however, they are able to correct for that movement and get back to where they started.
While a zebrafish is swimming 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 the scientists to search the entire brain to see which circuits are activated during their course-correcting behavior and disentangle the individual components involved.
The researchers expected to see activation in the forebrain – where the hippocampus, which contains a “cognitive map” of an animal’s environment, is located. 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 identified circuit via a hindbrain structure called the inferior olive to the motor circuits in the cerebellum that enable the fish to move. When these pathways were blocked, the fish was unable to navigate back to its original location.
This video shows a virtual reality environment of a zebrafish larva. Fish traverse a 2D environment in the presence of simulated water currents.Image credit: Misha Arens
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.
Reference: “Brainstem integrators of self-orientation memory and place homeostasis in zebrafish” by En Yang, Maarten F. Zwart, Ben James, Mikail Rubinov, Ziqiang Wei, Sujatha Narayan, Nikita Vladimirov, Brett D. Mensh, James E. Fitzgerald ” and Misha B. Ahrens, Dec. 22, 2022, cell.
DOI: 10.1016/j.cell.2022.11.022
