Cognition Without Cortex: Rapid Learning, Generalization, and Long-Term Memory in Acortical Mice
Date:
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Poster Abstract
Authors: Jieyu Zheng, Zeynep Turan, Katelyn Sadorf, Markus Meister; California Institute of Technology
In humans, the neocortex and hippocampus are central to memory, learning, and cognitive flexibility. To test whether these structures are similarly essential for rodent cognition, we studied an “acortical” mouse mutant born without the dorsal forebrain, lacking hippocampus and most of the neocortex. We tested these mice in two maze tasks: a complex binary-choice labyrinth and a massively reconfigurable arena called the Manhattan Maze. We probed four phases of learning across increasing timescales: exploration leading to reward discovery, rapid learning of an optimal route, long-term memory of the same environment, and generalization to novel mazes. Surprisingly, acortical mice were impaired only during the early exploration phase but retained other learning capacities. Despite delayed discovery of the reward location in the maze (~3× slower than controls), they exhibited one-shot learning of a short route to the reward, comparable to normal mice. They also rapidly obtained rewards when revisiting the same maze configurations after weeks-long and even months-long gaps. After learning the first maze, they solved new configurations more efficiently, generalizing across both acyclic and cyclic graph structures. Together, these results show that the absence of cortex and hippocampus slows the initial phase of exploration leading to a solution, but does not interfere with rapid exploitation of that solution, long-term memory, or generalization across similar tasks in the long run. We highlight the potential of subcortical circuits to support complex spatial cognition in mice, and suggest a more limited and specific role for the mouse hippocampus in the process of learning.
CCN 2024 conference information
Early Career Poster Session: Saturday, November 15, 6:45—8:45 p.m, Hall E of the San Diego Convention Center Poster Number B9
Regular Poster Session: Wednesday, November 19, 2025, 1:00 PM - 5:00 PM Poster Number SS5. Full information here
Videos
Acortical Mice in Manhattan: our latest video of one acortical mouse learning four different masks, over just three days!
[Wildtype and acortical mice respond to looming stimuli]
Documents
Download the poster here