Advances in understanding the molecular mechanisms mediating neuronal plasticity have provided important clues to the pathophysiology of drug abuse and addiction. Although substantial progress has been made in elucidating several key aspects of this process, e.g. the role of NMDA and AMPA receptors in mediating the induction and expression of activity-induced plasticity, respectively, critical features of this process are only partially understood. For example, it is now clear that enduring forms of synaptic plasticity require local translation of mRNAs that have been pre-positioned in the vicinity of synapses. However, we are only beginning to understand the mechanisms and molecules mediating mRNA trafficking and translation. In addition, recent studies have focused attention on the prevalence and importance of morphological changes associated with synaptic plasticity. However, how these changes occur and their relevance to functional plasticity are poorly defined. Accordingly, there is intense interest in understanding the molecular machinery that mediates and regulates these processes. To gain insights into these key features of synaptic plasticity, we plan to focus on two projects. In one, we will investigate the function and regulation of Tech, a RhoA GEF enriched in brain that has been implicated in regulating dendritic morphology. In the other, we will examine the role of the Translin/Trax RNA binding complex in mediating RNA trafficking in dendrites.
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