Macromolecular synthesis, distributed synaptic plasticity, and fear conditioning

Recent work from a number of laboratories has provided new and important insights about how gene expression is altered by experience and how these molecular changes may provide a substrate for the long-term storage of new memories. Here, we review a series of recent studies using aversive Pavlovian conditioning in rats as a well characterized model system in which experience-dependent alterations in gene expression can be manipulated and quantified within a specific neural circuit. We highlight some of the issues involved in using broad-spectrum inhibitors of mRNA and protein synthesis to study cellular changes underlying the formation and long-term stability of memory and discuss the idea that these changes occur over widespread, behaviorally-defined, networks of cells. We also discuss the idea that the maintenance of memory and its susceptibly to disruption after retrieval may relate to local protein synthesis in dendrites. Finally, a series of recent experiments from our laboratory studying the role of a specific signaling pathway (mTOR) which regulates translational processes and memory formation in the amygdala and hippocampus during fear conditioning are reviewed.