Translational control mechanisms in long-lasting synaptic plasticity and memory.

Mnemonic processes are controlled by selective modification (weakening or strengthening) of connections between neurons (1-5). To understand the precise molecular mechanisms by which this remarkably complex network encodes a given episode during learning is one of the major challenges in modern neuroscience (6). Two kinds of memory storage mechanisms have been described: short-term memory (STM), lasting only a few minutes or hours and long-term memory (LTM), which persists for many weeks, months, years and even a lifetime (7). Consolidation of LTM depends on de novo synthesis. Indeed, the first molecular distinction between STM and LTM emerged from studies with protein synthesis inhibitors more than 40 years ago: animals that were treated with drugs that block protein synthesis could not form LTM; yet, their STM was preserved. More than a century ago, Dr. Santiago Ramòn y Cajal, the great Spanish neuro-anatomist proposed that forming memories require neurons to strengthen their connections with one another. Now, it is widely accepted that information is stored in the brain as changes in the strength of synaptic connections. Like LTM, long-lasting, but not short-lasting changes, in the strength of synaptic connections depend on new protein synthesis. Such changes can be observed when neuronal activity is recorded in brain slices with microelectrodes in vitro.