Translational control of synaptic plasticity and learning and memory

One hallmark of long-term memory consolidation is the requirement for new gene expression. Although memory formation has largely focused on transcriptional control (Kandel 2001), it has been known for more than four decades that it also requires protein synthesis (Flexner et al. 1963). This and other early studies offered little in the way of molecular mechanisms because they relied mostly on the injection of general translation inhibitors into animals. The last 10 years, however, have witnessed major advances in our understanding of translational control of memory and its cellular foundation, synaptic plasticity. In this chapter, we discuss the most salient aspects of translational control of these essential brain activities and present our thoughts on some of the key issues remaining to be elucidated. TEMPORAL PHASES OF SYNAPTIC PLASTICITY AND MEMORY How are memories stored at the cellular level? Most neuroscientists hypothesize that memory involves changes in the strength of synaptic connections between neurons (i.e., synaptic transmission). These changes in synaptic efficacy are referred to as synaptic plasticity and are manifested as either an increase (potentiation) or decrease (depression) in strength. Long-term potentiation (LTP) and long-term depression (LTD) have been intensively studied in the rodent hippocampus, a brain structure that is critical for processing information about space, time, and the relationship between objects. Both LTP and LTD can be induced routinely in vitro with distinct patterns of electrical stimulation delivered to synapses in preparations of hippocampal slices. More than 20 years ago, hippocampal LTP was shown to require new protein synthesis...