The Entorhinal Cortex as a Gateway for Amygdala Influences on Memory Consolidation

The amygdala, specifically its basolateral nucleus (BLA), is a critical site integrating neuromodulatory influences on memory consolidation in other brain areas. Almost 20 years ago, we reported the first direct evidence that BLA activity is required for modulatory interventions in the entorhinal cortex (EC) to affect memory consolidation (Roesler, Roozendaal, and McGaugh, 2002). Since then, significant advances have been made in our understanding of how the EC participates in memory. For example, the characterization of grid cells specialized in processing spatial information in the medial EC (mEC) that act as major relayers of information to the hippocampus (HIP) has changed our view of memory processing by the EC; and the development of optogenetic technologies for manipulation of neuronal activity has recently enabled important new discoveries on the role of the BLA projections to the EC in memory. Here, we review the current evidence on interactions between the BLA and EC in synaptic plasticity and memory formation. The findings suggest that the EC may function as a gateway and mediator of modulatory influences from the BLA, which are then processed and relayed to the HIP. Through extensive reciprocal connections among the EC, HIP, and several cortical areas, information related to new memories is then consolidated by these multiple brain systems, through various molecular and cellular mechanisms acting in a distributed and highly concerted manner, during several hours after learning. A special note is made on the contribution by Ivan Izquierdo to our understanding of memory consolidation at the brain system level.