The findings challenge long-held assumptions about which brain regions are essential for spatial navigation and suggest that learning systems exist outside the cortex and hippocampus.
Acortical Mice Master the Manhattan Maze
Researchers studied mice lacking the PALS1 gene in the cells that give rise to the hippocampus and most of the cortex, preventing these structures from forming. These acortical mice initially struggled with the Manhattan Maze, a grid-like arena where they receive water at specific locations. They appeared anxious, scanned their surroundings repetitively, and took two to three times longer than control mice to obtain their first few rewards, said Jieyu Zheng, a graduate student in Markus Meister’s lab at the California Institute of Technology.
After that initial phase, however, the acortical mice learned, retained, and generalized the task at rates largely similar to control mice. When the maze was reconfigured, both groups adapted faster than they had during initial learning. “Obviously there is a system for learning and generalization that exists outside of cortex and hippocampus,” said Meister, professor of biological sciences at Caltech. “It is possible to perform navigation without a six-layered cortex.”
Spatial Information Appears Throughout the Brain
A separate preprint by an independent team found that typical mice carry spatial information across many brain regions, not just the hippocampus. Neurons that responded differently in the two halves of the corridor were deemed spatial, and such neurons appeared in every region recorded. A computational model could predict the mouse’s position from each area.
The hippocampal formation had roughly the same proportion of spatial cells as other regions, though it covered the corridor more uniformly. It encoded position less precisely than the visual cortex, however. “Now navigation is everywhere; decision-making is everywhere,” van Beest said. The work also suggests that different brain-wide networks may specialize in handling distinct memory tasks, and it remains unclear whether these networks overlap or are separate groups spread throughout the brain.
Brains Adapt Without Hippocampus
The results do not necessarily unseat the hippocampus as the primary center for navigation. Lisa Giocomo, professor of neurobiology at Stanford University, suggested the piriform cortex could help compensate, noting it shares the hippocampus’s laminar structure and is known for olfactory place coding.
It remains unclear whether typical mice rely on the same circuitry to learn the maze as the acortical mice. Lesion studies in adult rodents show that removing the hippocampus impairs spatial navigation, but those lesions tend to delay learning rather than abolish it, Zheng and Meister said. Some acortical mice never learned the task, possibly because the hippocampus helps initiate exploration. Potential candidates for the subcortical circuits guiding navigation include the superior colliculus, basal ganglia, and cerebellum, Meister said. Both teams plan to silence the hippocampus transiently in typical mice to test whether other regions can maintain spatial memory on their own.
FAQ: Questions About Brain Navigation in Mice
Can mice navigate without a hippocampus?
Yes. Mice born without a hippocampus and most of the neocortex learned the Manhattan Maze and remembered a nine-turn route three to four weeks later, though they were initially two to three times slower than control mice to obtain the first rewards.
Where is spatial information stored in a typical mouse brain?
Spatial neurons appeared in every region recorded, including the visual, motor, and somatosensory cortices, striatum, thalamus, and midbrain, as well as the hippocampal formation. The hippocampus covered space more uniformly but encoded position less precisely than the visual cortex.
Do normal mice use the same brain circuits as mice without a hippocampus?
That remains unclear. Both research teams plan to silence the hippocampus transiently in typical mice to test whether other brain regions can support spatial memory independently or are simply receiving input from the hippocampus.
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