Heterogeneous and specific synaptic localization of different mRNAs in neuronal dendrites

To facilitate rapid changes in protein composition in axons and dendrites, neurons can translate mRNAs into proteins at distal sites. This machinery requires long-range transport of specific mRNAs, which are packaged into granules by RNA-binding proteins and carried by kinesin motor proteins along microtubule. Local mRNA translation is crucial for dendritic spine development and plasticity. Nonetheless, whether different mRNAs are distributed in a specific manner near synapses and how is their localization regulated after synaptic stimulation are not well-characterized. Consistent with previous studies, we observed two prominent dendritic mRNAs, namely Actb and Camk2a, mostly appeared as separate granules in the dendrites. However, their colocalization became significantly higher underneath dendritic spines, suggesting this sub-dendritic compartment as the hotspot for mRNA delivery. Time-lapse imaging of the MS2-Actb mRNA reporter confirmed the restricted movement as well as specific docking of the mRNA granules at the base of dendritic spines. Activation of synaptic NMDA receptor after chemical long-term potentiation (cLTP) significantly reduced the co-localization of Actb and Camk2a mRNAs underneath dendritic spines. Notably, these two mRNAs exhibited distinct patterns of distribution at dendritic spines after cLTP. Our findings demonstrate that the dendritic spine base serves as the major sub-dendritic compartment to temporarily capture mRNAs, while different mRNAs can subsequently display selective synaptic targeting in response to activity.