Non-coding RNA in the wiring and remodeling of neural circuits

The brain constantly adapts to changes in the environment, a capability that underlies memory and behavior. Long-term adaptations require the remodeling of neural circuits that are mediated by activity-dependent alterations in gene expression. Over the last two decades, it has been shown that the expression of protein-coding genes is significantly regulated by a complex layer of non-coding RNA (ncRNA) interactions. The aim of this review is to summarize recent discoveries regarding the functional involvement of ncRNAs during different stages of neural circuit development, activity-dependent circuit remodeling, and circuit maladapations underlying neurological and neuropsychiatric disorders. In addition to the intensively studied microRNA (miRNA) family, we focus on more recently added ncRNA classes, such as long ncRNAs (lncRNAs) and circular RNAs (circRNAs), and discuss the complex regulatory interactions between these different RNAs. We conclude by discussing the potential relevance of ncRNAs for cell-type and -state-specific regulation in the context of memory formation, the evolution of human cognitive abilities, and the development of new diagnostic and therapeutic tools in brain disorders.