MicroRNA Regulation of Neuronal Differentiation and Plasticity

Abstract

MicroRNAs (miRNAs) expressed in the mammalian nervous system exhibit context-dependent functions during different stages of neuronal development, from early neurogenesis and neuronal differentiation to dendritic morphogenesis and neuronal plasticity. miRNAs often act through regulatory networks in specific cellular contexts and at specific times to ensure the progression through each biological state. Crosstalk between miRNAs and RNA-binding proteins introduces an additional layer of regulatory complexity in miRNA-mediated post-transcriptional regulation. Plasticity in localised parts of synapses is necessary for the information storage capacity of the brain. miRNAs and RNA-induced silencing complexes (RISCs) contribute to synaptic plasticity by modulating dendritic mRNA translation and dendritic spines. Specific molecules in neuronal cells may regulate miRNA action at the post-transcriptional and transcriptional level, suggesting that they may be involved in early and late responses underlying synaptic plasticity processes. Studies in animal models show that RISC and specific miRNAs may be recruited in synaptic plasticity processes underpinning learning, memory and cognition. Recent discoveries provide an encouraging starting point to investigate miRNA/RISC involvement in the development, progression and eventual therapeutic treatment of neurological and psychiatric diseases. Here we discuss recent findings that highlight the role of microRNAs in the regulatory networks associated with neuronal differentiation and synaptic plasticity in mammals.