Persistent up-regulation of polyribosomes at synapses during long-term memory, reconsolidation, and extinction of associative memory

Abstract

Local protein synthesis at synapses can provide a rapid supply of proteins to support synaptic changes during consolidation of new memories, but its role in the maintenance or updating of established memories is unknown. Consolidation requires new protein synthesis in the period immediately following learning, whereas established memories are resistant to protein synthesis inhibitors. We have previously reported that polyribosomes are up-regulated in the lateral amygdala (LA) during consolidation of aversive-cued Pavlovian conditioning. In this study, we used serial section electron microscopy reconstructions to determine whether the distribution of dendritic polyribosomes returns to baseline during the long-term memory phase. Relative to control groups, long-term memory was associated with up-regulation of polyribosomes throughout dendrites, including in dendritic spines of all sizes. Retrieval of a consolidated memory by presentation of a small number of cues induces a new, transient requirement for protein synthesis to maintain the memory, while presentation of a large number of cues results in extinction learning, forming a new memory. One hour after retrieval or extinction training, the distribution of dendritic polyribosomes was similar except in the smallest spines, which had more polyribosomes in the extinction group. Our results demonstrate that the effects of learning on dendritic polyribosomes are not restricted to the transient translation-dependent phase of memory formation. Cued Pavlovian conditioning induces persistent synapse strengthening in the LA that is not reversed by retrieval or extinction, and dendritic polyribosomes may therefore correlate generally with synapse strength as opposed to recent activity or transient translational processes.

Synapse-specific structural plasticity that protects and refines local circuits during LTP and LTD

“…Polyribosomes (PRs) have three or more ribosomes that form when mRNAs are unmasked and made available for local protein synthesis (figure 7g) [97][98][99][100]. PRs indicate locations where the synthesis of multiple copies of synaptic proteins occurs and where local circuits are enhanced, protected or refined during the saturation and recovery of LTP, learning and memory [101][102][103][104][105]. During LTP, PSDs on spines with polyribosomes undergo some enlargement that is greater than on spines without SER, but less than on spines with SER (figure 7h) [54,106].…”