Translational Regulatory Mechanisms in Persistent Forms of Synaptic Plasticity

Abstract

Memory and synaptic plasticity exhibit distinct temporal phases, with long-lasting forms distinguished by their dependence on macromolecular synthesis. Prevailing models for the molecular mechanisms underlying long-lasting synaptic plasticity have largely focused on transcriptional regulation. However, a growing body of evidence now supports a crucial role for neuronal activity-dependent mRNA translation, which may occur in dendrites for a subset of neuronal mRNAs. Recent work has begun to define the signaling mechanisms coupling synaptic activation to the protein synthesis machinery. The ERK and mTOR signaling pathways have been shown to regulate the activity of the general translational machinery, while the translation of particular classes of mRNAs is additionally controlled by gene-specific mechanisms. Rapid enhancement of the synthesis of a diverse array of neuronal proteins through such mechanisms provides the components necessary for persistent forms of LTP and LTD. These findings have important implications for the synapse specificity and associativity of protein synthesis-dependent changes in synaptic strength.

Acute 19-nortestosterone transiently suppresses hippocampal MAPK pathway and the phosphorylation of the NMDA receptor

“…1). Nevertheless, both ERKs and eIF4E play important roles in protein synthesis locally at synapses [25,26]. EphrinB2 at its synaptic localisation, is believed to be involved in synaptic plasticity [27], however in our fractions it is evenly distributed supporting the findings that it is also present in neuronal cell bodies in rodent hippocampus [28].…”

Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels

“…Interestingly, enhanced LTP in Trim3 −/− mice is confined to the early phase of LTP (i.e., the first 30 min after induction), which was previously demonstrated to also depend on protein synthesis (Fonseca et al, 2006). LTP maintenance is normal, suggesting that ACTG1 turnover may not be abolished completely in the absence of TRIM3 or that compensatory mechanisms that depend on gene expression and global protein synthesis (Kelleher et al, 2004) normalize plasticity at later time points. Hippocampal synapseenriched protein fractions were used as input for both immunoprecipitation (left) and polyubiquitin affinity pull-down (right).…”

Trimethylamine‐N‐oxide promotes brain aging and cognitive impairment in mice

“…Synaptic plasticity‐related proteins are a key component of the learning machinery in the brain (Iii et al., 2004). The expression levels of SYN, PSD‐95 and NMDAR1 were significantly decreased in P8‐C compared with R1‐C.…”

“…Activity‐dependent plasticity of neuronal connections represents the basis of learning and memory—the synaptic plasticity and memory (SPM) hypothesis (Iii, Govindarajan & Tonegawa, 2004; Squire & Davis, 1981). Mammalian target of rapamycin (mTOR) is a multifunctional and highly conserved serine/threonine kinase that has been shown to be a critical integrator of cell signalling in recent years (Sui, Wang & Li, 2008; Tischmeyer et al., 2003).…”