Neuron type-specific mRNA translation programs provide a gateway for memory consolidation.

Long-term memory consolidation is a dynamic process that requires a heterogeneous ensemble of neurons, each with a highly specialized molecular signature. Considerable effort has been devoted to identifying molecular changes that accompany the process of consolidation, but mostly hours or days after training, when memory consolidation is already complete. Studies have shown that protein synthesis is elevated during the early stages of consolidation, but how this increase impacts neuronal function remains unclear. We hypothesize that mRNAs translated during the early stages of consolidation could provide information on how diverse neurons involved in memory formation restructure their molecular signatures to support memory. Here, we generate a landscape of the translatome of three neuron types in the dorsal hippocampus during the first hour of contextual memory consolidation. Our results reveal that translation programs associated with consolidation are different among neurons, fueling the reconfiguration of specific biological processes. We further demonstrate the patterned translation of mRNAs in different neuron types during consolidation is explained by features hard-coded in the mRNA sequence, suggesting ubiquitous mechanisms controlling activity-induced neuronal translation. Altogether, our work uncovers previously unknown mechanisms controlling activity-induced translation in neurons and provides a large, readily available resource for scientists interested in the role of memory formation in health and disease.