Research Article: Early versus Late-Phase Consolidation of Opiate Reward Memories Requires Distinct Molecular and Temporal Mechanisms in the Amygdala-Prefrontal Cortical Pathway

Date Published: May 16, 2013

Publisher: Public Library of Science

Author(s): Shervin Gholizadeh, Ninglei Sun, Xavier De Jaeger, Melanie Bechard, Lique Coolen, Steven R. Laviolette, Lisa Carlson Lyons. http://doi.org/10.1371/journal.pone.0063612

Abstract

The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA) (early consolidation phase) to the medial prefrontal cortex (mPFC) (late consolidation phase). We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK)-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII), ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.

Partial Text

Opiates are powerfully addictive drugs that create potent associative memories. Indeed, the persistence of opiate addiction is in large part due to the ability of opiate-related memories to trigger compulsive drug seeking and relapse, even years after abstinence. Memory formation and recall is a complex process involving initial acquisition, consolidation and reconsolidation phases, each linked to unique molecular and neuroanatomical mechanisms [1], 2. Importantly, emotionally salient memories undergo reorganization in a temporally dependent manner, from a recently acquired, less stable trace, to a longer-term, more permanent representation following a process of consolidation [3], [4], [5]. However, the temporal, neuroanatomical and molecular mechanisms that control the consolidation of recent vs. remote drug-related reward memories are not currently understood.

Memory formation has been hypothesized to involve distinct temporal phases of encoding and consolidation. McGaugh [3] defined short-term memory, lasting minutes to hours, and a longer term memory process that consolidates slowly, representing a more permanent memory trace. Previous research has examined and dissociated the underlying neuronal and molecular substrates involved in recent vs. remote memory formation, particularly in the context of fear-related memories [2], [21]. This evidence has suggested functional relationships between the hippocampus and cortex as crucial for the transfer and consolidation of recent vs. remote associative memory [2]. In addition, re-activated fear-related memories undergo a labile period of reconsolidation during which time they are vulnerable to interference [7]. Interestingly, targeted protein synthesis inhibition, at least within the BLA, does not appear to disrupt the later recall of opiate-related reward memories but does block cocaine-associated reward memories [19], [25]. Nevertheless, the temporal and neuroanatomical characteristics of acute opiate reward memory consolidation have not previously been characterized.

Source:

http://doi.org/10.1371/journal.pone.0063612