#  Small RNA and RISC regulation of local translation and its role in memory 

 



We study how long-term memory is formed, focusing on mechanisms of synaptic plasticity that depend on local protein synthesis. We found that long-term memories form in association with mRNA transport and protein synthesis at particular synapses; that is, the modification of synapses is specific to the content of a memory. We also discovered a mechanism that regulates synaptic protein synthesis, involving microRNAs and the RISC pathway. In this mechanism, a neurotransmitter receptor associated protein called Rapsyn targets a RISC component, called Armitage, for Proteasome-mediated degradation. In addition, we have found that microRNA biogenesis is regulated by neural activity, and will determine whether this form of regulation occurs as memories form. To aid in this analysis, two-photon live imaging of Drosophila undergoing olfactory associative conditioning is being employed. To date, we have observed specific patterns of odor-induced synaptic output from the first order olfactory interneurons known as Projection Neurons, patterns that alter with associative conditioning. This preparation permits the manipulations of gene function and neural activity to be examined for effects on specific biochemical reporters, all during the induction of a memory. Our work has also opened up interesting avenues for translational research, including efforts to treat memory disorders and epilepsy. \[See publication, Ashraf et al., 2006; Patents Pending: “Compositions and Methods to Modulate Memory”\]