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The Journal of Neuroscience, December 13, 2006, 26(50):12977-12983; doi:10.1523/JNEUROSCI.4209-06.2006

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Behavioral/Systems/Cognitive
Translational Control via the Mammalian Target of Rapamycin Pathway Is Critical for the Formation and Stability of Long-Term Fear Memory in Amygdala Neurons

Ryan G. Parsons, ^* Georgette M. Gafford, ^* and Fred J. Helmstetter

Department of Psychology, University of Wisconsin–Milwaukee, Milwaukee, Wisconsin 53201

Correspondence should be addressed to Fred J. Helmstetter, Department of Psychology, University of Wisconsin–Milwaukee, Garland Hall, P.O. Box 413, Milwaukee, WI 53201. Email: fjh{at}uwm.edu

The mammalian target of rapamycin kinase (mTOR) regulates protein synthesis in neurons at the translational level through phosphorylation of several intracellular targets. Recent work in invertebrates indicates that mTOR-dependent translational control may be critical for the induction and maintenance of activity-dependent synaptic plasticity underlying memory formation. Here, we report that training rats in a simple fear conditioning procedure evokes a time-dependent increase in the phosphorylation of p70s6 kinase, a major direct downstream target of mTOR. When the activation of mTOR was prevented by posttraining injection of rapamycin into the amygdala, formation of the memory and the increase in p70s6 kinase phosphorylation was attenuated. Furthermore, when rapamycin was applied to the amygdala after the recall of a previously stored fear memory, subsequent retention was disrupted, indicating that local translational control at active synapses is required for the stability as well as the formation of long-term memory in this system.

Key words: reconsolidation; consolidation; local protein synthesis; translational control; synaptic plasticity; fear conditioning

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Received Sept. 26, 2006; revised Nov. 3, 2006; accepted Nov. 4, 2006.

Correspondence should be addressed to Fred J. Helmstetter, Department of Psychology, University of Wisconsin–Milwaukee, Garland Hall, P.O. Box 413, Milwaukee, WI 53201. Email: fjh{at}uwm.edu

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