Summary
Long-term memory consolidation is a dynamic process that requires a heterogeneous ensemble of neurons, each with a highly specialized molecular environment. Considerable effort has been placed into understanding how the molecular mechanisms in specific neuron types are modified in memory, but these studies are often undertaken hours or days after training, when memory is already consolidated. Studies have shown that protein synthesis is elevated during the early stages of consolidation, but there is limited information as to how it impacts neuronal function. We hypothesize that mRNAs being translated during the early stages of consolidation could provide clues as to how diverse neurons involved in memory formation restructure their molecular architecture to support memory formation. 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 show that these neurons share a common backbone of readily translated mRNAs. However, excitatory neurons undergo deep reconfiguration of proteostatic control, whereas interneurons modify their synaptic transmission. We demonstrate that the translational control in these neurons requires GADD34, which promotes translation initiation. Finally, we show that the differential expression of mRNAs by neurons during early consolidation can be explained by features hard coded in the mRNA, suggesting ubiquitous mechanisms controlling activity-dependent neuronal translation. Altogether, our work uncovers previously unknown checkpoints controlling activity-dependent translation in neurons and provides a large, readily available resource for further investigations of memory formation in health and disease.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵# Co-second authors
