Role of mTORC1 and protein translation in memory consolidation in the neocortex

Medial-temporal lobe (MTL) input to layer 1 (L1) of the neocortex is crucial for memory consolidation. Based on our own preliminary data we hypothesize that protein synthesis and upstream mTORC1 activity are required for MTL-dependent plasticity and therefore underlie learning in the neocortex. We will test this hypothesis by combining genetic and pharmacological manipulations with biochemical and cell biological approaches to study the impact of altered protein synthesis or mTORC1 activity on MTL-gated memory consolidation. Specifically, we will investigate the reliance of MTL-gated memory consolidation on local mTORC1-regulated protein synthesis in the tuft dendrites of layer 5 (L5) pyramidal neurons or in somatostatin-positive interneurons. Moreover, we will examine the molecular events that are induced by an enriched environment (EE) known to facilitate learning and memory consolidation. We expect these studies to provide insights into the molecular mechanisms for memory formation and consolidation in a defined behavioral paradigm and location.