• associative memory
• Lateral Entorhinal Cortex
• LTD
• LTP
• Synaptic Plasticity

The entorhinal cortex represents a major hub between the hippocampal formation and polymodal associative areas and, based on cytoarchitecture, connectivity and function, it can be subdivided into two main subregions: the lateral and the medial entorhinal cortex (LEC and MEC respectively). Interestingly, the LEC has been shown to play a role in the formation of object-place-context associative learning. However, changes in synaptic plasticity induced by associative learning in the intrinsic circuitry of the LEC have not been investigated. Here, we used the object-place-context recognition test (OPCRT) as behavioural paradigm and we characterized the time course of this specific memory performing the sample trials at time 0 and presenting the test trial 1h, 6h, 12h or 24h following the presentation of the sample trials. OPCRT-dependent activation of the LEC neurons was confirmed by immunofluorescence staining for the immediate early gene c-fos. Moreover, we recorded field excitatory post-synaptic potentials in LEC superficial layers using brain slices obtained from mice subjected to OPCRT and we found that the main forms of synaptic plasticity, namely LTP and LTD, were altered following behaviour, inducing changes in the intrinsic circuitry of LEC superficial layers. Specifically, LTP was reduced in mice subjected to OPCRT compared to control ones, and LTD was enhanced, suggesting that the formation of this associative memory is able to induce a shift in the threshold for synaptic modifications. These results confirm the involvement of the LEC superficial layer plasticity in the OPCRT paradigm and encourage us to further investigate the specific role of LEC neurons in the formation and retrieval of associative memories.