The Role of Ribosome Biogenesis in Learning and Memory

Abstract

Active ribosomes, producing new proteins, have been interrogated nearly since the beginning of the molecular analysis of memory. These studies of ribosomal function have been extremely fruitful in determining individual proteins and molecular pathways important for memory formation. For the vast majority of this work, ribosomes have been considered readily available: A distributed organelle able to translate throughout the cell with specificity being determined by distinct regulators.This is not an unreasonable assumption as ribosomes are long lived and were believed to homogenous. Recently, our group and others have begun to uncover data that challenge these assumptions. We have previously shown that new ribosomes are required for synaptic plasticity, a neuronal process thought to underly memory, while another group has shown that the approximately 200 genes that code for RNA component of the ribosome are not homogenous, and in fact,are differentially regulated across cell type. Building on these findings, we sought to investigate the role of synthesis of new ribosomes in learning and memory. Presented here are data showing that transcription of only one variant of the RNA component of the ribosome is induced by learning in mice, and that the new ribosomes made from these transcripts are necessary for memory formation. This implies that the new ribosomes are necessary because they are qualitatively different from old ribosomes. What's more, pharmacological up-regulation of both ribosome activity and ribosome biogenesis can enhance memory formation in mice. This enhancement is dependent on new ribosomes. Further studies are needed to figure out how these new ribosomes are different from the existing pool, and what functionality those differences allow.