Transcriptomic analysis identifies synapse-enriched lncRNAs required for excitatory synapse development and fear memory

Abstract

SummaryRegulatory functions of lncRNAs in neurons have been majorly limited to the nucleus. The identity of synaptic lncRNAs and their functional role associated with synapse development and memory are poorly understood. We employed RNA-seq analysis of synaptoneurosomes to identify 94 synapse-enriched lncRNAs from the mouse hippocampus. We find Pvt1 to be a specific regulator of excitatory, but not inhibitory, synapse developmentin vivo. RNA-Seq from Pvt1 knockdown neurons identified down-regulated transcripts encoding pre- and post-synaptic proteins influencing synapse formation. This observation is congruent with reduction in mEPSC amplitude and frequency. We find a synapse-centric role for SynLAMP which is specifically transported to the synaptic compartment upon contextual fear conditioning (CFC) and regulate activity-dependent dendritic translation. CFC led to enhancement of interaction between SynLAMP and the translation repressor FUS, indicating SynLAMP to be a molecular decoy. SynLAMP RNAi partially occludes fear memory, suggesting an input-specific role of lncRNAs at the synapse.