MicroRNAs are important regulators of local protein synthesis during neuronal development. We investigated the dynamic regulation of microRNA production and found that the majority of the microRNA‐generating complex, consisting of Dicer, TRBP, and PACT, specifically associates with intracellular membranes in developing neurons. Stimulation with brain‐derived neurotrophic factor (BDNF), which promotes dendritogenesis, caused the redistribution of TRBP from the endoplasmic reticulum into the cytoplasm, and its dissociation from Dicer, in a Ca2+‐dependent manner. As a result, the processing of a subset of neuronal precursor microRNAs, among them the dendritically localized pre‐miR16, was impaired. Decreased production of miR‐16‐5p, which targeted the BDNF mRNA itself, was rescued by expression of a membrane‐targeted TRBP. Moreover, miR‐16‐5p or membrane‐targeted TRBP expression blocked BDNF‐induced dendritogenesis, demonstrating the importance of neuronal TRBP dynamics for activity‐dependent neuronal development. We propose that neurons employ specialized mechanisms to modulate local gene expression in dendrites, via the dynamic regulation of microRNA biogenesis factors at intracellular membranes of the endoplasmic reticulum, which in turn is crucial for neuronal dendrite complexity and therefore neuronal circuit formation and function.
Progress in microscopy technology has a long history of triggering major advances in neuroscience. Super-resolution microscopy (SRM), famous for shattering the diffraction barrier of light microscopy, is no exception. SRM gives access to anatomical designs and dynamics of nanostructures, which are impossible to resolve using conventional light microscopy, from the elaborate anatomy of neurons and glial cells, to the organelles and molecules inside of them. In this review, we will mainly focus on a particular SRM technique (STED microscopy), and explain a series of technical developments we have made over the years to make it practical and viable in the field of neuroscience. We will also highlight several neurobiological findings on the dynamic structure-function relationship of neurons and glia cells, which illustrate the value of live-cell STED microscopy, especially when combined with other modern approaches to investigate the nanoscale behavior of brain cells.
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