Translational control in synaptic plasticity and cognitive dysfunction

Shelly Buffington, Wei Huang, Mauro Costa-Mattioli

Research output: Contribution to journalReview article

148 Scopus citations

Abstract

Activity-dependent changes in the strength of synaptic connections are fundamental to the formation and maintenance of memory. The mechanisms underlying persistent changes in synaptic strength in the hippocampus, specifically long-term potentiation and depression, depend on new protein synthesis. Such changes are thought to be orchestrated by engaging the signaling pathways that regulate mRNA translation in neurons. In this review, we discuss the key regulatory pathways that govern translational control in response to synaptic activity and the mRNA populations that are specifically targeted by these pathways. The critical contribution of regulatory control over new protein synthesis to proper cognitive function is underscored by human disorders associated with either silencing or mutation of genes encoding proteins that directly regulate translation. In light of these clinical implications, we also consider the therapeutic potential of targeting dysregulated translational control to treat cognitive disorders of synaptic dysfunction. ©

Original languageEnglish (US)
Pages (from-to)17-38
Number of pages22
JournalAnnual Review of Neuroscience
Volume37
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Keywords

  • Autism
  • EIF2α
  • Local protein synthesis
  • Memory
  • MTOR
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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