In this study, we found that rodents that acquire contextual fear memories in the absence of the dorsal hippocampus fail to express these memories as they become remote. These data suggest that contextual fear memories formed in the absence of the dorsal hippocampus may lack the persistence of those formed with the hippocampus intact. In line with previous findings, they show that animals can overcome the amnestic effects of pre-training DH lesions provided adequate training is given (Wiltgen, et al., 2006
). However, our results are the first to reveal that the ability to overcome anterograde amnesia may be dependent on the length of time between training and test, such that recently acquired contextual fear memories remain intact while the expression of such memories at remote time points is dramatically impaired. Thus, explicit memories formed using alternate, compensatory structures seem to lack the permanence characteristic of normal contextual fear memories (Gale, et al., 2004
). One way to interpret these findings is that contextual fear memories formed in the absence of the DH are unable to be consolidated in the same way as those formed with the DH intact.
These findings suggest that even when contextual fear memories rely on regions outside the DH for initial memory formation, the hippocampus is vital for the transformation of these memories from a recent to remote state. That is, the DH may be required for the long-term consolidation of explicit memories, regardless of the structure in which these memories were initially established. Thus, the properties required of an explicit memory in order for it to be subject to cellular consolidation may not necessarily be sufficient for that memory to be permanently consolidated.
We demonstrate that in order for a contextual fear memory to become permanent the DH must be intact. This implies that the compensatory structures recruited in the absence of the DH are incapable of permanently holding onto these memories, suggesting that they are more fragile in nature. The involvement of the DH in the ability for long-term memories to be stored permanently is supported by studies showing that memories formed in the remote past can be disrupted by blocking CA3 output, therein disturbing the integrity of the tri-synaptic pathway and the ripple-associated reactivation of hippocampal memory (Nakashiba, et al., 2009
). Additionally, it has been shown that the prefrontal cortex is phase-locked to hippocampal theta (Siapas, et al., 2005
) and that ablation of NMDARs on interneurons (Korotkova, et al., 2010
) or blockade of electrical communication between interneurons in the hippocampus (Bissiere, et al., 2011
) disrupts hippocampal synchrony and hippocampus-dependent memory. These findings support the idea that an intact hippocampus is essential for the permanent consolidation of a memory or at the least, that memories formed using alternate circuitry are not formed in neuronal ensembles that have access to the appropriate synchrony, electrical communication or intracellular signaling properties required for stable storage.
Surprisingly, the straightforward prediction that memories formed in the absence of the hippocampus lack permanence has never been tested. Two factors likely contribute to the difficulty in conducting such a test. One is that as the retention interval between training and testing increases, normal forgetting in the intact controls can obscure a failure of systems consolidation with hippocampal damage (Zola-Morgan & Squire, 1990
). A second issue is that tasks that take several days to acquire do not allow a clear separation between the period of acquisition and systems consolidation. Thus, an ideal task to test for the longevity of memories is one that can both be acquired in a single brief session and is stable across time. By using contextual fear conditioning, we were able to employ a task that satisfied both these requirements.
Lastly, our findings dovetail nicely with those previously reported examining contextual fear in the absence of the basolateral amygdala (BLA). That is, the BLA is integral to fear learning and memory (Fanselow & LeDoux, 1999
) and damage to the BLA results in a massive deficit in fear acquisition and expression (Maren, et al., 1996
). However, animals are able to learn and express context fear following BLA damage, provided they are trained using a very robust acquisition protocol (Maren, 1999
; Ponnusamy, et al., 2007
; Poulos, et al., 2010
). In addition, contextual fear memories formed in the absence of the BLA do not persist across time (Poulos, et al., 2009
). Thus, our results for the DH parallel those found for the BLA, suggesting that both the DH and BLA are essential components of the circuitry required for a contextual fear memory to become permanent.
These findings imply a general conclusion about compensation following brain damage: namely, that learning and memory can occur in the absence of the relevant primary structure(s), but that learning is less efficient and that the memories formed decay with time. Therefore, when the primary circuit for a specific task is compromised, not only does it seem to be a general property of the brain that an alternate circuit be recruited to compensate (Fanselow, 2010
), but it may also be a general finding that these compensatory memories fade with time. While further experiments examining whether the same pattern is maintained across different hippocampus-dependent tasks and preparations are warranted, the question is most relevant in situations where expression of memory remains unabated with time.
These results also have important clinical implications. They suggest that memories normally thought to involve the hippocampus may be formed following hippocampal damage, but that these memories are more fragile, failing to persist across time. Thus, clinical approaches towards reducing or overcoming amnesia could benefit from developing methods to promote the longevity of memories formed following brain damage. Such advances would be facilitated by the identification of the brain regions underlying contextual memories formed in the absence of the hippocampus.