A consistent map in the medial entorhinal cortex supports spatial memory

Taylor J. Malone, Nai-Wen Tien, Yan Ma, Lian Cui, Shangru Lyu, Garret Wang, Duc Nguyen, Kai Zhang, Maxym V. Myroshnychenko, Jean Tyan, Joshua A. Gordon, David A. Kupferschmidt and Yi Gu ()
Additional contact information
Taylor J. Malone: National Institutes of Health
Nai-Wen Tien: National Institutes of Health
Yan Ma: National Institutes of Health
Lian Cui: National Institutes of Health
Shangru Lyu: National Institutes of Health
Garret Wang: National Institutes of Health
Duc Nguyen: National Institutes of Health
Kai Zhang: National Institutes of Health
Maxym V. Myroshnychenko: National Institute of Mental Health, National Institutes of Health
Jean Tyan: National Institutes of Health
Joshua A. Gordon: National Institute of Mental Health, National Institutes of Health
David A. Kupferschmidt: National Institute of Mental Health, National Institutes of Health
Yi Gu: National Institutes of Health

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract The medial entorhinal cortex (MEC) is hypothesized to function as a cognitive map for memory-guided navigation. How this map develops during learning and influences memory remains unclear. By imaging MEC calcium dynamics while mice successfully learned a novel virtual environment over ten days, we discovered that the dynamics gradually became more spatially consistent and then stabilized. Additionally, grid cells in the MEC not only exhibited improved spatial tuning consistency, but also maintained stable phase relationships, suggesting a network mechanism involving synaptic plasticity and rigid recurrent connectivity to shape grid cell activity during learning. Increased c-Fos expression in the MEC in novel environments further supports the induction of synaptic plasticity. Unsuccessful learning lacked these activity features, indicating that a consistent map is specific for effective spatial memory. Finally, optogenetically disrupting spatial consistency of the map impaired memory-guided navigation in a well-learned environment. Thus, we demonstrate that the establishment of a spatially consistent MEC map across learning both correlates with, and is necessary for, successful spatial memory.

Date: 2024
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DOI: 10.1038/s41467-024-45853-4

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