An outstanding question is whether memory consolidation occurs passively or involves active processes that selectively stabilize memories based on future utility. Here, we differentially modulated the expected future relevance of two sets of picture-location associations after learning. Participants first studied two sets of picture-location associations. After a baseline memory test, they were instructed that only one set of associations would be retested after a 14-hour delay. For half of the participants, this test-retest delay contained a night of sleep; for the other half the delay included a normal working day. At retest, participants were re-instructed and against their expectations tested on both sets of associations. Our results show that post-learning instruction about subsequent relevance selectively improves memory retention for specific associative memories. This effect was sleep-dependent; it was present only in the group of subjects for which the test-retest delay contained sleep. Moreover, time spent asleep for participants in this sleep group correlated with retention of relevant but not irrelevant associations; participants who slept longer forgot fewer associations from the relevant category. In contrast, participants that did not sleep forgot more relevant than irrelevant associations across the test-retest delay. In summary, our results indicate that it is possible to modulate the retention of selected memories after learning with simple verbal instructions on their future relevance. The finding that this effect depends on sleep demonstrates this state’s active role in memory consolidation and may have utility for educational settings.

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a parahippocampal area, which decreased with time. In turn, mPFC-parahippocampal connectivity increased progressively. These findings support a model in which thalamic midline nuclei serve as a hub linking hippocampus, mPFC, and posterior representational areas during memory retrieval at an early (2 h) stage of consolidation, extending classical systems consolidation models by attributing a transient role to midline thalamic nuclei.The standard model of systems consolidation (e.g., Alvarez and Squire 1994) describes an initial stage in which the hippocampus binds together distributed neocortical representations during retrieval of recent memories. These neocortical representations code event features that are located in sensory-specific and multimodal representational areas in posterior parts of the brain, which are engaged during initial encoding. With consolidation, interconnectivity between these representational areas stabilizes, allowing retrieval of remote memories to be hippocampally independent. Accumulating evidence from animal and human work has extended this view by showing evidence for medial prefrontal cortex (mPFC) involvement during remote memory retrieval (Bontempi et al. 1999;Takashima et al. 2006; TakeharaNishiuchi and McNaughton 2008). The mPFC appears interacting with posterior representational areas during retrieval of remote memories (Frankland and Bontempi 2005), potentially binding them together (Takashima et al. 2006;Wheeler et al. 2013).The systems-level processes underlying this transition from a hippocampally to a neocortically dependent memory are not well understood, though there seems evidence for a hippocampalmPFC interaction underlying this process (van Kesteren et al. 2010). However, rodent hippocampal-mPFC fibers are unidirectional and rather unevenly distributed over the hippocampus (Vertes et al. 2007;Hoover and Vertes 2012) and thus, an indirect interaction appears necessary if a bidirectional information flow between mPFC and hippocampus is required during systems consolidation. The rat's thalamic midline structures (nucleus reuniens/rhomboid nucleus) are reciprocally connected to both the mPFC and hippocampus as well as to posterior representational areas (Aggleton and Brown 1999;Van der Werf et al. 2002;Vertes et al. 2006Vertes et al. , 2007Hoover and Vertes 2012;Cassel et al. 2013;Wheeler et al. 2013) that seems also evident in nonhuman primates (Amaral and Cowan 1980;DeVito 1980;Aggleton et al. 1986Aggleton et al. , 2011Hsu and Price 2007). Indeed, the nucleus reuniens acts as a hippocampal-mPFC relay during memory encoding in mice determining specificity/generalization of memory attributes (Xu and Südhof 2013). The nucleus reuniens seems als...

The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long‐term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ‐aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face–name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory‐related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory‐related functional connectivity in a medial prefrontal–thalamus–hippocampus network.