Layer 5 lateral entorhinal cortex neurons encode updating of object-place associations

Associative recognition memory is essential for everyday life, forming cognitive representations of and recalling relationships between things we encounter and their environments. Object place associations are represented in the lateral entorhinal and medial prefrontal cortices, however the identity of neurons in which these associations are formed, the cellular mechanisms supporting them, and how these representations react to change are not understood. Here we labelled associative recognition memory engrams, finding that engram neuron reactivation by memory recall correlated with behavioural performance only in the dorsolateral subregion of entorhinal cortex, where reactivation was overrepresented in layer 5/6. Electrophysiology from ex vivo slices prepared directly following memory recall revealed increased excitability in layer 5 lateral entorhinal cortex engram cells, which only occurred when engram-specific objects were reconfigured. These data identify deep layer lateral entorhinal cortex neurons as key loci of object-place associations and proposes a plastic mechanism by which pre-existing neural representations are updated.