Changes in patterns of neural activity underlie a time‐dependent transformation of memory in rats and humans

Abstract

The dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time-dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context-specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal-frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually-detailed as well as less precise, schematic memories. These findings provide cross-species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation.

Reminders reinstate context-specificity to generalized remote memories in rats: relation to activity in the hippocampus and aCC

“…It follows from this that the aCC should exhibit relatively low activity levels following retrieval of the recently reactivated memory. The second, based on our group's previous results, is that aCC activity is high during remote memory retrieval in either context, as the reorganized memory trace in the cortex comes online to support the generalized remote memory representation in the healthy brain under normal physiological conditions (Sekeres et al 2018a).…”

“…Over time, memories in rats that were once highly specific to the contextual cues present during memory acquisition are changed as the memory transforms from one that is critically dependent upon the hippocampus, to one that becomes supported by both the hippocampus and the prefrontal cortex, particularly anterior cingulate cortex (aCC) (Frankland et al 2004;Wiltgen and Silva 2007;Winocur et al 2007;Einarsson and Nader, 2012;Wheeler et al 2013;Cullen et al 2015;Einarsson et al 2015;Kitamura et al 2017;Vetere et al 2017;Sekeres et al 2018a;DeNardo et al 2019;Ortiz et al 2019). Reactivating an established 30 d old fear memory by presenting the contextual cues that were present during encoding reinstates context-specificity to the remote memory (Sekeres et al 2012), and renders the memory sensitive to hippocampal disruption during the postreactivation reconsolidation window (Debiec et al 2002).…”

“…It remains unknown how aCC-hippocampal patterns of activity interact at the cellular level in the intact brain to support retrieval of a recently reactivated remote context memory under natural conditions (for reviews, see Hardt and Nadel 2018;Sekeres et al 2018b). Considerable evidence suggests that reactivating a remote fear memory should result in high hippocampal activity following retrieval in the original conditioning context but not in a novel context (Wiltgen et al 2010;Sekeres et al 2018a). With respect to the aCC, two outcomes are possible.…”

“…With respect to the aCC, two outcomes are possible. The first is based on evidence that aCC activity, and the type of memory representation it develops over time, are insensitive to differences in retrieval context (Cullen et al 2015;Einarsson et al 2015;Sekeres et al 2018a). It follows from this that the aCC should exhibit relatively low activity levels following retrieval of the recently reactivated memory.…”

“…See Figure 1A for a schematic of the study design. Following previously reported procedures (Winocur et al 2007(Winocur et al , 2009(Winocur et al , 2013Sekeres et al 2018a), each rat was given a 30 min context preexposure session in the conditioning chamber. Twentyfour hours later, each rat was given ten tone-shock pairings (tone: 2000 Hz; 90 dB, 30 sec; shock: 1.5 mA, 1 sec) in the conditioning chamber (Context-A).…”