The entorhinal cortex is thought to be the first region affected i n Alzheimer's disease. The region is a part of the medial temporal lobe memo ry system, relaying information between the hippocampus and association area s throughout the neocortex. Damage to the circuits of entorhinal cortex duri ng early stages of Alzheimer's disease is therefore likely to be responsible for the initial development of memory impairments. This talk will present s everal studies that examined how the entorhinal cortex dynamically interacts with the medial prefrontal cortex and hippocampus to support the expression of long-term memories. First, using trace eyeblink conditioning in rats as a model of associative memory, I will show that lateral portions of the ento rhinal cortex play a long-lasting role in memory retrieval, and that this ro le depends on the region's connection with the medial prefrontal cortex. Sec ond, I will present recordings of local field potentials collected from late ral entorhinal and medial prefrontal cortices, as well as from the hippocamp us, suggesting that communication between these regions changes over the cou rse of learning. The results emphasize that the role of the entorhinal corte x in memory depends on its interactions with the hippocampus and other regio ns of neocortex, providing a locus for future attempts to model the neural b asis of memory impairments accompanying Alzheimer’s disease.