Silc1 long noncoding RNA is an immediate-early gene promoting efficient memory formation

Long noncoding RNAs (lncRNAs) are expressed in many brain circuits and types of neurons; nevertheless, their functional significance for normal brain functions remains elusive. Here, we study the functions in the central nervous system of Silc1, an lncRNA we have shown previously to be important for neuronal regeneration in the peripheral nervous system. We found that Silc1 is rapidly and strongly induced in the hippocampus upon exposure to novelty and is required for efficient spatial learning. Silc1 production is important for induction of Sox11 (its cis-regulated target gene) throughout the CA1–CA3 regions and proper expression of key Sox11 target genes. Consistent with its role in neuronal plasticity, Silc1 levels decline during aging and in models of Alzheimer’s disease. Overall, we describe a plasticity pathway in which Silc1 acts as an immediate-early gene to activate Sox11 and induce a neuronal growth-associated transcriptional program important for learning.