Researchers discover new functions of the ‘ancient brain’

Clarify the brain

The hindbrain is a region of the brain that controls basic vital functions such as heart rate, breathing, and balance. The hindbrain is the most primitive part of the brain and serves as a major link between the spinal cord and higher brain regions.

A multi-regional hindbrain circuit enables animals to regain their trajectory after deviating from it.

The zebrafish heads towards its target, but the strong currents push it off course. Undeterred, the little fish returned to its 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 in Howard Hughes Medical Institute The 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 next.

New research recently published in the journal cellreveals new functions for parts of the “old brain”, findings that may apply to others[{” attribute=””>vertebrates.

Zebrafish Whole Brain Imaging

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 for zebrafish larvae. Fish traverse a two-dimensional environment with simulated water flow. Credit: Mischa Ahrens

These results indicate that regions of the brainstem remember the zebrafish’s original location and generate an error signal based on their current and previous locations. This information is transmitted to the cerebellum, which allows the fish to return to its starting point. This research reveals a new function for the inferior olive and cerebellum, which were known to be involved in actions such as reaching and locomotion, but not this type of locomotion.

“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 the motor control centers so that the fish can correct after being moved by flow unintentionally, even after many seconds.”

New multidirectional circle

It remains unclear whether these same networks are involved in similar behavior in other animals. But the researchers hope that labs that study mammals will now start looking in the hindbrain for symmetric circuits for navigation.

Researchers say this hindbrain network could also be the basis for other navigational skills, such as when a fish swims to a specific location for shelter.

“This is a circuit so unknown for this form of navigation that we think may underlie higher-order hippocampal circuits for exploration and feature-based navigation,” says Misha Arens, senior group leader at Janelia.

Reference: “Brainstem integrators of self-location memory and postural balance in zebrafish” by En Yang, Martin F. Zwart, Ben James, Mikael Robinov, Zhiqiang Wei, Sujata Narayan, Nikita Vladimirov, Brett de Mensch, James E. Fitzgerald and Misha P. Ahrens, Dec. 22, 2022, Available here. cell.
DOI: 10.1016/j.cell.2022.11.022

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