A multiregional brain circuit allows larval zebrafish to track where they are, where they’ve been, and how to return to their original location after being displaced, researchers report Dec. 22 in the journal Cell. The results highlight how larval zebrafish track their own location and use it to navigate after being pushed off course by currents.
“We studied a behavior where larval zebrafish must remember previous displacements to correctly maintain their location in space because, for example, water flow can sweep them into dangerous areas in their natural environment,” said senior author Misha Ahrens of Janelia Research Campus, Howard Hughes Medical Institute . “Yet it is unknown whether they explicitly track their location over long time scales and use memorized positional information to return to their previous location—a behavior we call positional homeostasis. Such abilities may be ethologically critical because larval zebrafish swim intermittently and are moved by currents. during rest .”
Many animals keep track of where they are in their environment. They use self-location information for many important behaviors, such as efficiently returning to safe locations after visiting unfamiliar and potentially dangerous areas, revisiting food-rich areas, and avoiding foraging in food-poor areas. Although self-localization is represented in the hippocampal formation, it is unknown how such representations arise, whether they reside in older brain regions, and by which pathways they control movement.
“Such circuits have been difficult to pin down because neuroscience typically relies on recordings from cells in preselected brain regions that cover a small portion of all neurons in the brain,” said first author En Yang of Janelia Research Campus, Howard Hughes Medical Institute.
In the new study, the researchers set out to identify complete navigation circuits in larval zebrafish, from movement integrators to premotor centers, by comprehensively imaging and analyzing the whole brain at cellular resolution during self-localization behavior. Access to more than 100,000 neurons per animal revealed brain regions previously unknown to be involved in self-localization, leading to the discovery of a multiregional hindbrain circuit that mediates a transformation from speed, through displacement memory, to behavior.
“Our results reveal a neural system for self-localization and associated behavior in the vertebrate hindbrain and provide a circuit-level, representation, and control-theoretic understanding of its function. The system operates in a closed loop with dynamic environments, and the environment-brain-behavior loop includes integration, neural representations of self-localization and motor control,” Ahrens says. “These findings demonstrate the need to consider brains at a holistic level and to unify systems neuroscientific concepts—such as self-localization and motor control—that are often studied separately.”
Whole-brain functional imaging revealed not only the existence of positional homeostasis in larval zebrafish, but also how the brain identifies and corrects changes in zebrafish location. The underlying circuitry computes self-localization in the dorsal brainstem by integrating visual information to form a memory of past displacements when the animal actively or passively changes its location. This self-location representation is read out by the inferior olive as a long-term position error signal, reflecting the difference between the fish’s original and current position. This signal is converted into motion power that corrects for accumulated displacements over the course of many seconds.
The authors state that this multiregional circuit has potential anatomical and functional homologues in mammals and may interact with other known representations of self-localization. Furthermore, this work links self-localization and olivocerebellar motor control and establishes the vertebrate hindbrain as a neural control center for goal-directed navigational behavior.
“Our results on place memory and positional homeostasis resonate with the idea that evolutionarily ancient brain regions contribute centrally to higher-order behaviors,” says Ahrens. “The idea that cognitive processes are widely distributed across the nervous system is consistent with the evolutionary proposition that complex behaviors arose in part by building new circuits on top of ancient brain structures that perform related computations. Brain-wide investigations of neural activity may thus be crucial to determining the mechanisms of distributed cognitive feature.”
This work was supported by the Howard Hughes Medical Institute and by the Simons Foundation.
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