Localized mRNAs and protein synthesis in cortical layer 1

Cortical layer 1 plays an essential role in neural networks, integrating many streams of information and undergoing plasticity during learning. Yet, we know little about the underlying molecular processes and whether layer-specific adaptations exist. Here, we show that layer 1 and its synapses actively synthesize proteins. Using laser capture RNA-sequencing and fluorescence in situ hybridization, we report an abundance of localized synaptic transcripts. We purify layer 1 excitatory and inhibitory mouse synapses and characterize their enriched transcriptomes, identifying proteins that can be locally synthesized and finding significant differences with deeper layer transcriptomes. Finally, we discover a strong similarity between cortical layer 1 and hippocampal stratum lacunosum moleculare, which suggests a conserved molecular architecture of these distal layers. Together, our results establish local protein synthesis as an important feature of cortical layer 1, and we provide the first comprehensive description of the transcriptomes of layer 1 and its synapses, which we make available online.