Memory formation is thought to be encoded by alterations in the effectiveness of synaptic connections between neurons. Electrophysiological and behavioral studies have demonstrated that long-lasting synaptic plasticity requires protein synthesis. However, changes in efficacy of an individual synapse can occur independently of other synapses on the same cell, raising the question of how this specificity is achieved on a molecular level. One possibility is that local protein translation within dendrites contributes to alterations in synaptic efficacy. Although most mRNA species are restricted to the cell soma, a small subset have also been found in dendrites, including the mRNA encoding the alpha subunit of calcium-calmodulin dependent protein kinase type II (CaMKIIalpha). To investigate the functional significance of this dendritic localization gene targeting has been used to disrupt the signal in the 3' untranslated region (3'UTR) of CaMKIIalpha mRNA which controls its localization. In this knockout mouse the coding region of the mRNA is intact but its localization is restricted to cell bodies. The two specific aims proposed for the competitive renewal are as follows: I. Characterize the role of dendritic translation of CaMKIIalpha in determining the localization of the CaMKIIalpha protein. II. Determine whether synaptic and behavioral plasticity are affected by disruption of the dendritic localization of CaMKIIalpha mRNA. These experiments will provide insight into the role of dendritic translation in memory formation. Characterization of the basic mechanisms contributing to memory is a requisite step in identifying the molecular and cellular etiology of each of the various pathological conditions in which memory is affected.
