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

Abstract

AbstractLong noncoding RNAs (lncRNAs) are expressed in many brain circuits and neuronal types, but their significance to normal brain functions has remained largely unknown. Here, we study the functions in the central nervous system ofSilc1, a lncRNA we previously showed to be important for neuroregeneration in the peripheral nervous system. We found thatSilc1is rapidly and strongly induced upon stimulation in the hippocampus and is required for efficient spatial learning.Silc1production is important for the induction ofSox11(its cis-regulated target gene) throughout the CA1-CA3 regions and the proper expression of keySox11target genes. Consistent with its newly found role in neuronal plasticity, we find that during aging and in models of Alzheimer’s diseaseSilc1levels decline. Overall, we uncover a novel plasticity pathway, in whichSilc1acts as an immediate-early gene to activateSox11to induce a neuronal growth-associated transcriptional program important for memory formation.