Consolidation and translation regulation: Figure 1.

Abstract

mRNA translation, or protein synthesis, is a major component of the transformation of the genetic code into any cellular activity. This complicated, multistep process is divided into three phases: initiation, elongation, and termination. Initiation is the step at which the ribosome is recruited to the mRNA, and is regarded as the major rate-limiting step in translation, while elongation consists of the elongation of the polypeptide chain; both steps are frequent targets for regulation, which is defined as a change in the rate of translation of an mRNA per unit time. In the normal brain, control of translation is a key mechanism for regulation of memory and synaptic plasticity consolidation, i.e., the off-line processing of acquired information. These regulation processes may differ between different brain structures or neuronal populations. Moreover, dysregulation of translation leads to pathological brain function such as memory impairment. Both normal and abnormal function of the translation machinery is believed to lead to translational up-regulation or down-regulation of a subset of mRNAs. However, the identification of these newly synthesized proteins and determination of the rates of protein synthesis or degradation taking place in different neuronal types and compartments at different time points in the brain demand new proteomic methods and system biology approaches. Here, we discuss in detail the relationship between translation regulation and memory or synaptic plasticity consolidation while focusing on a model of cortical-dependent taste learning task and hippocampal-dependent plasticity. In addition, we describe a novel systems biology perspective to better describe consolidation.

Phosphorylation of Eukaryotic Translation Initiation Factor 4E and Eukaryotic Translation Initiation Factor 4E-binding Protein (4EBP) and Their Upstream Signaling Components Undergo Diurnal Oscillation in the Mouse Hippocampus

“…Consolidation of hippocampus-dependent memory and various forms of long-lasting synaptic plasticity depend on new protein synthesis (38,39). However, it seems unlikely that a single round of translation generated during memory acquisition can account for the persistence of LTM, which persists for periods exceeding the lifetime of synaptic proteins generated during memory formation.…”

Signaling pathways controlling activity-dependent local translation of BDNF and their localization in dendritic arbors

“…Initiation is considered the major rate-limiting step of translational regulation during which mRNA and ribosome start their interaction and cap-dependent initiation factors are recruited (Gal-Ben-Ari et al, 2012;Santini and Klann, 2014). We investigated eiF4E because it is the main limiting factor of the cap-dependent initiation.…”

Consolidação do tempo na memória de longo prazo: fatores facilitadores e interferentes

“…This is based on the fact that synaptic and cellular mechanisms involved in the local storage of a memory trace include several cascades of molecular events, such as the synthesis of new proteins, that take time (from minutes to hours). This has been now well described in animals for a number of memory tasks (see Gal-Ben-Ari et al, 2012;. In our study, we observed this dissociation between long-term and short-term effects for memory of duration in humans.…”

“…The memory traces thus consolidate slowly over time. Research in animals, using pharmacological agents, has shown that cellular/synaptic consolidation requires messenger ribonucleic acid (mRNA) translation and synthesis of new proteins, mechanisms which take time to be completed (e.g., Alberini, Milekic & Tronel, 2006;Gal-Ben-Ari et al, 2012;McGaugh, 1989;Schafe, Nader, Blair & LeDoux, 2001). Thus, two memory systems have been dissociated pharmacologically: (1) a short-term memory, which maintains information from a few seconds to several minutes and which is independent of new protein synthesis, from (2) a long-term memory for hours-to-months maintenance.…”