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.
Helmstetter
Fred J
FJ
Department of Psychology, University of Wisconsin, P.O. Box 413, Milwaukee, WI 53201, USA. fjh@uwm.edu
Parsons
Ryan G
RG
Gafford
Georgette M
GM
D000679:Amygdala / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D005239:Fear; D015870:Gene Expression / Q000235:genetics; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D009415:Nerve Net / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D015533:Transcriptional Activation / Q000235:genetics
D046912:Multiprotein Complexes; D012333:RNA, Messenger; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases