mTOR and the Regulation of Translational Capacity in Late Forms of Synaptic Plasticity

Abstract

Stimulus-induced changes in gene expression, mediated by translation and transcription, are required for persistent forms of synaptic plasticity (late-LTP and late-LTD) and for memory consolidation. In recent years, the search for the translational control mechanisms that operate during synaptic plasticity has centered on signaling within the dendritic compartment, guided by the accumulating evidence that proteins synthesized within dendrites, and not in the cell body, are required for late-LTP and late-LTD. Among the fi rst such control mechanisms to be discovered was the activation of mechanistic target of rapamycin (mTOR; formerly called mammalian TOR), a ubiquitous translational regulator that is required for the induction of late-LTP and late-LTD. The consistent requirement of mTOR in multiple forms of late plasticity suggests that it is involved in the synthesis of both LTPand LTD-related plasticity-related proteins (PRPs).This chapter focuses on the importance of mTOR-regulated translational capacity in neurons and other cells that must rapidly synthesize proteins in response to appropriate stimuli. The role of mTOR in synaptic plasticity, and the potential mechanisms by which synaptic activity activates mTOR, are addressed. We review the behavioral studies that established the relevance of mTOR to long-term memory (LTM), including the consolidation and reconsolidation of hippocampus-dependent LTM, and the acquisition and expression of drug-seeking behavior. Finally, we outline a model of synaptic capture in which activation of mTOR raises the