Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit

Abstract

Remote memory usually decreases over time, whereas remote drug-cue associated memory exhibits enhancement, increasing the risk of relapse during abstinence. Memory system consolidation is a prerequisite for remote memory formation, but neurobiological underpinnings of the role of consolidation in the enhancement of remote drug memory are unclear. Here, we found that remote cocaine-cue associated memory was enhanced in rats that underwent self-administration training, together with a progressive increase in the response of prelimbic cortex (PrL) CaMK neurons to cues. System consolidation was required for the enhancement of remote cocaine memory through PrL CaMK neurons during the early period post-training. Furthermore, dendritic spine maturation in the PrL relied on the basolateral amygdala (BLA) input during the early period of consolidation, contributing to remote memory enhancement. These ndings indicate that memory consolidation drives the enhancement of remote cocaine memory through a time-dependently increase in activity and maturation of PrL CaMK neurons receiving a sustained BLA input.