Regulating RNA in space and time in memory circuits

Localization of mRNAs to neuronal terminals, coupled to local translation, has emerged as a prevalent mechanism dynamically controlling the synaptic proteome. However, the physiological regulation and function of this process in the context of mature in vivo memory circuits has remained unclear. Here, we combined synaptosome RNA profiling with whole brain high-resolution imaging to uncover mRNAs with different localization patterns in the axons of Drosophila memory neurons, some exhibiting regionalized, input-dependent, recruitment along axons. By integrating transcriptome-wide binding approaches and functional assays, we identified a conserved machinery controlling the transport of mRNAs to Mushroom Body axons and characterize a mutant in which this transport is selectively impaired. Using this unique mutant, we demonstrate that axonal mRNA localization is required for long-term, but not short-term, behavioral memory. This work uncovers circuit-dependent mRNA targeting in vivo and demonstrates the importance of local RNA regulation in memory consolidation.