Malone Taylor J, Tien Nai-Wen, Ma Yan, Cui Lian, Lyu Shangru, Wang Garret, Nguyen Duc, Zhang Kai, Myroshnychenko Maxym V, Tyan Jean, Gordon Joshua A, Kupferschmidt David A, Gu Yi
Spatial Navigation and Memory Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
These authors contributed equally to this work.
bioRxiv. 2023 Oct 2:2023.09.30.560254. doi: 10.1101/2023.09.30.560254.
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.
内侧内嗅皮层（MEC）被假定为作为记忆引导导航的认知地图发挥作用。该地图在学习过程中如何发展以及如何影响记忆仍不清楚。通过在小鼠在十天内成功学习新的虚拟环境时对MEC钙动力学进行成像，我们发现动力学逐渐变得在空间上更加一致，然后稳定下来。此外，MEC中的网格细胞不仅表现出改善的空间调谐一致性，而且还保持稳定的相位关系，这表明存在一种涉及突触可塑性和刚性循环连接的网络机制，以在学习过程中塑造网格细胞活动。在新环境中MEC中c-Fos表达的增加进一步支持了突触可塑性的诱导。不成功的学习缺乏这些活动特征，表明一致的地图对于有效的空间记忆是特定的。最后，光遗传学破坏地图的空间一致性会损害在熟悉环境中记忆引导的导航。因此，我们证明跨学习建立空间一致的MEC地图既与成功的空间记忆相关，也是成功的空间记忆所必需的。
