microRNAs (miRNAs) are novel gene circuitry regulators with an elusive role in neuronal development and plasticity. These small non-coding RNA molecules may explain some of the dysfunctional mechanisms in mental disorders, and are promising targets for diagnosis and treatment of neuropsychiatric disorders. I have recently identified pre-synaptically enriched miRNAs, of which miR-338 was found to modulate the mitochondrial function. This fellowship will allow me to use the knowledge I have gained on the roles of synaptic translation in neuronal development and plasticity as a Research Associate in USA and implement that knowledge to Europe. The three main objectives of my proposed research are: (1) to identify candidate miRNAs differentially expressed during hippocampal development and plasticity; (2) to delineate miRNA’s regulatory role on local protein synthesis which is required for synaptic plasticity; and (3) to determine the functions of miRNAs in neuronal development and plasticity. To address objectives 1 and 2, I will employ deep-sequencing to identify miRNA genes differentially and spatially expressed during experience-dependent synaptic plasticity in the rat hippocampus and its synaptic compartments, respectively, and carry out computational prediction followed by experimental confirmations to identify miRNAs involved in synaptic function. In objective 3, I will investigate miRNA function in different forms of synaptic plasticity using cell biological approaches combined with in vivo behavioral experiments. I anticipate that my interdisciplinary research approach will define the role of miRNAs in synaptic plasticity and memory storage. The research proposed is innovative and significant because it may establish a new avenue of research on synaptic pathophysiology in mental disorders, and may provide the European society with cutting-edge technology with the potential to generate new miRNA-based therapies to treat nervous system disorders.
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