Reproducible and predictable reorganization of place fields driven by grid subfield rate changes.

Understanding how the brain constructs stable yet flexible maps of space remains a central challenge in neuroscience. Place cells in the hippocampus fire at specific locations in a given environment, but reorganize completely upon introduction to another environment in a process called remapping. The medial entorhinal cortex (MEC) provides a major cortical input to the hippocampus, and the spatially periodic firing patterns of its grid cells are thought to contribute to place field formation. We previously showed that chemogenetic depolarization of MEC layer II stellate cells selectively altered firing rates within individual grid cell subfields, impaired spatial memory, and induced a form of reversible place cell remapping that we called artificial remapping. However, it remains unclear whether artificial remapping reflects a reproducible and stable mapping from entorhinal inputs to place cell outputs or a random reorganization of place fields. To explore the transfer of information between MEC and hippocampus, we repeated this chemogenetic manipulation on consecutive days and found that stimulating the same stellate cells produced similar changes in both grid subfield rates and place field locations. Using both experimental and simulated data, we show that baseline place cell activity patterns could be used to predict place field locations following the manipulation. These findings provide direct evidence for consistent input-output relationships in the entorhinal-hippocampal system and point to a central role for grid subfield rate changes in the reorganization of hippocampal spatial representations.