The Hippocampus Plays a Selective Role in the Retrieval of Detailed Contextual Memories

Abstract

Summary Background It is widely believed that the hippocampus plays a temporary role in the retrieval of episodic and contextual memories. Initial research indicated that damage to this structure produced amnesia for newly acquired memories but did not affect those formed in the distant past. A number of recent studies, however, have found that the hippocampus is required for the retrieval of episodic and contextual memories regardless of their age. These findings are currently the subject of intense debate and a satisfying resolution has yet to be identified. Results The current experiments address this issue by demonstrating that detailed memories always require the hippocampus while memories that lose precision become independent of this structure. First, we show that the dorsal hippocampus is preferentially activated by the retrieval of detailed context fear memories. We then establish a causal relationship between the hippocampus and detailed memories using a context generalization procedure. Mice that exhibit high levels of generalization to a novel environment show no memory loss when the hippocampus is subsequently inactivated. In contrast, mice that discriminate between contexts are significantly impaired by hippocampus inactivation. Conclusions Our data suggest that detailed context memories always require the hippocampus (independent of their age) while memories that lose precision can be retrieved without this structure. These findings account for inconsistencies in the literature - memories of our distant past can be either lost or retained after hippocampus damage depending on their quality – and provide a new framework for understanding memory consolidation. Highlights The retrieval of new context fear memories increases immediate early gene expression in the hippocampus. Immediate early gene expression decreases as memories age and become less precise. If memory is tested at a single retention interval, hippocampus inactivation selectively impairs the retrieval of precise context memories.

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

“…Our observation of increased involvement of the ACC in remote memory is in line with previous research showing that, over time (after 2 weeks in rodents), the ACC becomes more involved in supporting contextual fear memory (Frankland et al, 2004;Goshen et al, 2011), whereas at the same time the involvement of the hippocampus is reduced (Anagnostaras et al, 1999;de Oliveira Alvares et al, 2012;Goshen et al, 2011;Kitamura et al, 2009;Ward et al, 1999;Wiltgen et al, 2010;Winocur et al, 2009). Our findings are also consistent with the idea that the hippocampus is critical for integrating information in a distributed cortical network representing various features of a memory, but as the memory trace matures, the ACC gradually takes over this integrative role and becomes critical for the expression of remote memory (Frankland and Bontempi, 2005).…”

“…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.…”

“…Contextual memories are known to become less precise in the weeks following learning in rodents (Biedenkapp and Rudy, 2007;Riccio et al, 1992;Ruediger et al, 2011;Wiltgen et al, 2010;Winocur et al, 2009;Winocur et al, 2007), such that animals increasingly generalize the conditioned response to a novel context similar to the training context, and eventually show comparable conditioned responding to both contexts. In light of our findings that suppressing neural activity in the ACC by blocking AMPA/kainate receptors was ineffective in disrupting contextual fear expression in the original training context 6 h following remote memory reactivation, we next tested if AMPA/ kainate-receptor blockade in the ACC at this time point would affect generalized contextual fear memory expression.…”

“…Lesions or pharmacological inactivation of the hippocampus preferentially impact recently acquired contextual fear memory (Anagnostaras et al, 1999;de Oliveira Alvares et al, 2012;Goshen et al, 2011;Kitamura et al, 2009;Ward et al, 1999;Wiltgen et al, 2010;Winocur et al, 2009). Conversely, transient disruption of the anterior cingulate cortex (ACC) impairs the expression of remote, but not recent memory (Frankland et al, 2004;Goshen et al, 2011).…”

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).…”