Protein Synthesis and Memory

The need for training-initiated protein synthesis for memory formation is the prevalent view for mechanisms of memory consolidation. This theory states that memory passes through at least two phases after an experience: a protein synthesis-independent phase that lasts for a few hours after training and a protein synthesis-dependent phase in which new proteins are produced after training are responsible for the ultimate neuronal changes that store and then maintain memory for that learned event. However, this purported fundamental property of memory formation is not fully supported by many findings and is actually contradicted by some of those findings. This chapter reviews many of these discrepancies, some based on recent results confirming findings obtained decades ago and some based on novel findings. Topics include the following: (1) studies of the time-limited phases of memory formation based on protein synthesis inhibitors that reveal a very wide range of times, from seconds to weeks, for memory formation; (2) there are many examples showing that training and synaptic plasticity are not always impaired by protein synthesis inhibitors; (3) many treatments rescue memory impaired by protein synthesis inhibitors while not interfering with the ability of these inhibitors to block protein synthesis; and (4) Specific neurobiological consequences of protein synthesis inhibition, in addition to more specific side effects of various protein synthesis inhibitors, appear to mediate the effects of the inhibitors on memory. Taken together the evidence points to a weak foundation for a theory of memory formation based on an early protein synthesis-independent phase of memory followed by a protein synthesis-dependent phase of memory. Instead, these experiments provide information about mechanisms mediating amnesia, which need not be the inverse of the mechanisms underlying memory.