Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.
The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation. New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation.
Center for Neural Science, New York University, New York, USA.
Emanuela
E
Santini
Center for Neural Science, New York University, New York, USA.
Thu N
TN
Huynh
Center for Neural Science, New York University, New York, USA.
Eric
E
Klann
D000818:Animals; D006801:Humans; D017774:Long-Term Potentiation; D000076222:Mechanistic Target of Rapamycin Complex 1; D057567:Memory, Long-Term / Q000502:physiology*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D014176:Protein Biosynthesis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
4E-BP; Consolidation; Long-term potentiation; Memory; Protein synthesis; S6K1; eIF2α; eIF4E; mTOR