Fine-tuning of gene expression is a fundamental requirement for development and maintenance of neuronal networks in our brain. Neurons require both stability and flexibility to function in connections to other cells by complex networks via thousands of synapses. In the proposed project we will study how local protein translation at the synapse is regulated by small non-coding miRNAs in a global perspective. A novel methodology based on high throughput sequencing will be used to determine specific interactions between miRNAs and their target mRNAs in purified synaptic buds. Further analyses will be done to verify these regulatory events in primary neuronal cultures. Regulation of local gene expression is of particular importance during synapse formation and activation. The role of microRNAs in this regulation and how miRNA maturation is controlled will also be explored. miRNAs have been implicated in a wide range of biological functions from embryonic development to aging. The proposed project will not only increase our understanding of synaptic function, it will also increase our understanding in general of how local subcellular gene expression can be controlled by non-coding RNAs.