The regulation of protein synthesis has been shown to have a central role in synaptic plasticity, which is thought to underlie learning and memory. This regulation has been shown to occur through the action of cytoplasmic polyadenylation element binding protein (CPEB), which controls the length of the mRNA's poly(A) tail and translational status. Mice deficient for CPEB have alterations in long term potentiation and memory consolidation. The direct molecular cause(s) of these phenotypes, however, is unknown. With the long-term objective of gaining insight into the function of translational regulation in learning and memory, the hypothesis that CPEB affects the translation of multiple mRNAs in neurons in response to synaptic activation will be tested. The research design utilizes microarray analysis of polysomal RNAs from wild type and CPEB deficient mice to identify mRNAs that are translationally regulated by CPEB. Additionally, several candidates will be tested. The polyadenylation and translational regulation of the mRNAs in response to synapse activation will then be established using binding and polyadenylation assays and stimulation of cultured hippocampal neurons.
