Memory for context becomes less specific with time

Abstract

Context memories initially require the hippocampus, but over time become independent of this structure. This shift reflects a consolidation process whereby memories are gradually stored in distributed regions of the cortex. The function of this process is thought to be the extraction of statistical regularities and general knowledge from specific experiences. The current study examined this idea in mice by measuring the specificity of context memories during consolidation. In the first experiment, separate groups of animals were trained with a single shock and tested in the training context or a novel environment 1, 14, 28, or 36 d later. We found a systematic increase in generalization over this period. Initially, mice froze more in the training context, but fear of the novel environment grew over time until animals eventually froze an equivalent amount in both contexts. The second experiment demonstrated that the increase in generalization was due to a loss of detailed information about the context and not fear incubation. In this experiment, mice were exposed to the context and then trained with an immediate shock 1 or 36 d later. Animals trained 1 d after exposure acquired robust context fear that did not generalize across environments. In contrast, mice trained 36 d after exposure froze an equivalent amount in the training context and the novel environment. The same profile was observed in H-ras mutants that exhibit enhanced hippocampal plasticity and learning. These results suggest that context memories are specific early after training when they require the hippocampus, and become more general as they are permanently stored in the cortex.The hippocampus plays a time-limited role in the retrieval of memory. Damage to this structure produces a loss of recently formed memories and leaves intact those acquired in the remote past (Anagnostaras et al. 1999;Squire et al. 2004;Bayley et al. 2005). As memory becomes independent of the hippocampus, it is thought to be permanently stored in distributed regions of the cortex (Squire and Alvarez 1995;Squire et al. 2004;Wiltgen et al. 2004;Frankland and Bontempi 2005). Consistent with this idea, recent animal studies showed activation of cortical sites and a concurrent deactivation of the hippocampus when old memories were retrieved. Pharmacological inactivation of these same cortical regions during retrieval produced a selective remote memory deficit (Bontempi et al. 1999;Frankland et al. 2004a;Maviel et al. 2004).Contemporary learning models suggest this reorganization of memory systems reflects an important process, the extraction of statistical regularities, and general knowledge from specific experiences (McClelland et al. 1995;O'Reilly and Rudy 2001). According to these models, the hippocampus rapidly encodes detailed memories (i.e., episodes) and then replays them so that the cortex can slowly extract features that are common across experiences (i.e., semantic memories). Consistent with this idea, episodic memory retrieval in humans includes a detailed reexperie...

Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear

“…These findings are in line with what is seen in GABA B(1a) KO mice; they display precise memory recall for contextual fear or object recognition 2 h, but not 24 h after training (Cullen et al, 2014). Several studies demonstrate the importance of the hippocampus in context memory precision (Ruediger et al, 2011;Wiltgen and Silva, 2007;Wiltgen et al, 2010;Winocur et al, 2007). According to the transformation hypothesis of memory function over time, detailed context-specific memories are initially dependent on the hippocampus, but are transformed into schematic (less specific) memories as they are stored in the neocortex, resulting in generalized memory recall (Frankland et al, 2006;Frankland et al, 2001;Kim and Fanselow, 1992;McGaugh, 1966;Vetere et al, 2011;ZolaMorgan and Squire, 1990).…”

“…To date, theories of memory precision all share the idea that the passage of time is required in order for generalized responding to occur (Biedenkapp and Rudy, 2007;Jasnow et al, 2012;Lynch et al, 2013;Matynia et al, 2008;Wiltgen and Silva, 2007;Winocur et al, 2007). The current data suggest, in some cases, the loss of memory precision does not require a significant passage of time (ie, several or more days) and can be dependent upon the maintenance of the originally formed memory trace during memory consolidation.…”

Disruptive Effect of Midazolam on Fear Memory Reconsolidation: Decisive Influence of Reactivation Time Span and Memory Age

“…Interestingly, fear was absent early after training, but it was evident in remote memories, when animals were exposed to a novel context. As previously proposed (Wiltgen and Silva, 2007), this suggests that contextual fear memories generalize to other environments with the passage of time. In addition, MDZ administration after exposure to the nonassociated environment does not affect fear memory regardless of the interval between training and exposure to B.…”

Systems Reconsolidation Reveals a Selective Role for the Anterior Cingulate Cortex in Generalized Contextual Fear Memory Expression

“…A number of studies have described how contextual fear memory becomes less context-specific over time, showing that animals increasingly generalize conditioned responding to novel contexts (Biedenkapp and Rudy, 2007;Ruediger et al, 2011;Wiltgen and Silva, 2007;Wiltgen et al, 2010;Winocur et al, 2009;Winocur et al, 2007). Similarly, we found that rats did not generalize conditioned fear responding to a novel context when tested 3 days after training, but expressed generalized fear in the novel context when tested 30 days after training.…”

“…This posited role of the hippocampus in supporting context memory precision is supported by recent studies showing (a) that inactivation of the dorsal hippocampus disrupts the expression of context-specific fear memory, but not the expression of generalized fear memory (de Oliveira Alvares et al, 2012;Wiltgen et al, 2010) and (b) that inhibitory connectivity in the mossy fibers of the dorsal hippocampus are critical for maintaining context-specificity of contextual fear memory (Ruediger et al, 2011). Previous studies have demonstrated that brief re-exposure to a training context at remote time points can reinstate context-specific memory expression, an effect that lasts from 1 h (Zhou and Riccio, 1994), up to at least 24 h (Wiltgen and Silva, 2007). This brief reversal of fear generalization may be mediated by a transient recruitment of the hippocampus, possibly as part of a memory updating process.…”