Local translation in perisynaptic astrocytic processes is specific and regulated by fear conditioning

Local translation is a conserved molecular mechanism conferring cells the ability to quickly respond to local stimuli. It not only permits cells with complex morphology to bypass somatic protein synthesis and transport, but also contributes locally to the establishment of molecular and functional polarity. In the brain, local translation has been extensively studied in neurons and has only been recently reported in astrocytes, whose fine processes contact both blood vessels and synapses. Yet the specificity and regulation of astrocyte local translation remain unknown. Here, we studied hippocampal perisynaptic astrocytic processes (PAPs) and show that they contain all the machinery for translation. Using our recently refined polysome immunoprecipitation technique, we then characterized the pool of polysomal mRNAs in PAPs, referred to as the PAPome, and compared it to the one found in the whole astrocyte. We found that the PAPome encoded an unexpected molecular repertoire, mostly composed of cytoplasmic proteins and of proteins involved in iron homeostasis, translation, cell cycle and cytoskeleton. Among them, ezrin (Ezr), ferritin heavy chain 1 (Fth1) and 60S acidic ribosomal protein1 (Rplp1) were enriched in PAPs compared to perivascular astrocytic processes, indicating that local translation differs at these two interfaces. Remarkably, PAPs were also enriched in transcripts coding for proteins involved in learning and memory, such as ferritin (Ftl1 and Fth1), G1/S-specific cyclin-D2 (Ccnd2), E3 ubiquitin-protein ligase (Mdm2), Receptor of activated protein C kinase 1 (Gnb2l1) and Elongation factor 1-alpha 1 (Eef1a1). To address their regulation in a physiological context, we assessed their local translation after fear conditioning. We found alterations in their density and/or distribution in astrocytes as well as a drop in their translation specifically in PAPs. In all, our results reveal an unexpected molecular repertoire of hippocampal PAPs, which is regulated by local translation during learning and memory processes.