Medial prefrontal cortex input to lateral entorhinal cortex supports both encoding and retrieval of associative recognition memory

Associative recognition memory allows us to form representations of items and their environment and to judge the novelty of such representations. This memory is dependent on a brain circuit that includes interactions between medial prefrontal cortex (mPFC) and lateral entorhinal cortex (LEC); however it is unknown whether the interaction of these brain areas is required for memory encoding, retrieval or both processes. Furthermore, little is known as to whether indirect or direct mPFC-LEC connections are critical for associative recognition memory and, if the latter, in which direction information travels. To address these questions, we first performed pharmacological disconnection of mPFC and LEC, finding that mPFC-LEC interaction is required for both memory encoding and retrieval. Next, we optogenetically inhibited projections from mPFC to LEC, showing that this projection was crucial for both encoding and retrieval of both object-in-place and object-in-context recognition memory when a 1 h, but not a 5 min, memory retention delay was used. These data show that a direct connection from mPFC to LEC is critical for associative recognition memory, in a delay-dependent manner.