Dendritic protein synthesis and synaptic plasticity

Brown University, Providence RI

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Abstract

The persistent modification of the brain by experience is the neural basis for learning and memory. A wealth of data suggest that an important site of experience-dependent modification is the synapse, and that the induction and persistence of synaptic modifications depend importantly upon new protein synthesis. It has also been established that synaptic activity can regulate gene transcription, the synapse-specific capturing of newly synthesized proteins, and the synapse-specific translation of existing mRNAs. However, precisely how these varied mechanisms contribute to synaptic plasticity remains unresolved. One major goal of this project is to investigate which modes of protein synthesis control are used for two different forms of synaptic plasticity, one in the hippocampus (mGluR-dependent LTD) and the other in the visual cortex (experience-dependent changes in NMDARs). A second major goal is to investigate the functional significance of one specific mechanism for the local synaptic control of mRNA translation, cytoplasmic polyadenylation. Thus, the work has both "top-down" and "bottom-up" components. The "top-down" component starts with two forms of protein-synthesis dependent synaptic plasticity, and dissects their mechanisms. The "bottom-up" component starts with a mechanism for translation regulation, and assesses its contributions to synaptic plasticity and memory.