Chadney, O. M. T.; Guardamagna, M.; Dorr, F.; Descamps, L. A. L.; Stella, F.; Battaglia, F.; Kentros, C. G.

The hippocampus and its main input, the entorhinal cortex, are essential for memory formation, yet how they interact to do so remains unresolved. Hippocampal CA1 pyramidal neurons exhibit spatial receptive fields which reorganize unpredictably upon exposure to a novel environment, a process called remapping, considered a model of memory formation. CA1 neurons integrate both hippocampal and direct entorhinal inputs, but their relative contributions to spatial coding are unclear. Here we combined population recordings of CA1 neurons with optogenetic silencing of their direct entorhinal input. While this manipulation did not impact spatial firing in a familiar environment, it impaired remapping in a novel environment, resulting in the emergence of a stable hybrid map combining features of both environments. This shows the direct entorhinal pathway plays a specific role in CA1 novelty detection, enabling the plasticity necessary to drive the reorganisation of spatial firing patterns, preventing interference between memories in different contexts.