Hippocampus and retrograde amnesia in the rat model: a modest proposal for the situation of systems consolidation

Abstract

The properties of retrograde amnesia after damage to the hippocampus have been explicated with some success using a rat model of human medial temporal lobe amnesia. We review the results of this experimental work with rats focusing on several areas of consensus in this growing literature. We evaluate the theoretically significant hypothesis that hippocampal retrograde amnesia normally exhibits a temporal gradient, affecting recent, but sparing remote memories. Surprisingly, the evidence does not provide much support for the idea that there is a lengthy process of systems consolidation following a learning episode. Instead, recent and remote memories tend to be equally affected. The extent of damage to the hippocampus is a significant factor in this work since it is likely that spared hippocampal tissue can support at least partial memory retrieval. With extensive hippocampal damage gradients are flat or, in the case of memory tasks with flavour/odour retrieval cues, the retrograde amnesia covers a period of about 1-3 days. There is consistent evidence that at the time of learning the hippocampus interferes with or overshadows memory acquisition by other systems. This contributes to the breadth and severity of retrograde amnesia relative to anterograde amnesia in the rat. The fact that multiple, distributed learning episodes can overcome this overshadowing is consistent with a parallel dual-store theory or a Distributed Reinstatement Theory in which each learning episode triggers a short period of memory replay that provides a brief hippocampal-dependent systems consolidation.

Figure 1

Evidence from our laboratory that complete HPC damage in rats has dissociable effects on anterograde and retrograde memory in contextual fear conditioning. Complete damage made to the HPC before a single contextual fear conditioning session (Anterograde) did not cause anterograde amnesia, suggesting that, in absence of the HPC, non-HPC memory systems can readily acquire and support the memory for successful performance on the retention test. However, complete HPC damage induced 1–3 days after a single contextual fear conditioning session (Retrograde) almost abolished freezing during the retention test, suggesting profound retrograde amnesia and that contextual fear conditioning is normally dependent on the HPC. That contextual fear conditioning is normally dependent on the HPC, but can be supported by non-HPC memory systems in absence of the HPC implies that in the intact brain the HPC and non-HPC systems interact and that the HPC overshadows or prevents the non-HPC systems from acquiring an independent memory.

Figure 2

Mean (+ SEM) percent time freezing during a retention test by Sham and HPC rats that received either a single or repeated contextual fear conditioning sessions before surgery. Complete HPC damage after a single (massed) contextual fear conditioning session that involved 12 foot shocks given within 17 min caused a significant freezing impairment (p < .05), suggesting that the damage caused severe retrograde amnesia and that the memory is dependent on the HPC. Oppositely, rats that received complete HPC damage after repeated conditioning sessions distributed across 6 days, which also in total involved 12 shocks and 17 minutes within the conditioning context, did not freeze significantly less than their respective control group (p > .05). Moreover, the HPC rats from the repeated condition showed significantly more freezing than the HPC rats from the single condition (p < .05). Hence, repeated conditioning sessions prevented the retrograde amnesic effects of complete HPC damage, implying that non-HPC systems were able to establish an HPC-independent memory and that repeated learning sessions mitigated the HPC overshadowing. The findings are adapted from and are fully described in Lehmann et al. (2009).

Figure 3

Mean (+ SEM) novel object investigation ratio during an object recognition retention test by Sham and HPC rats that received 5, 10, or 30 sample/learning sessions before surgery. Complete HPC damage induced 3–5 days after 5 sample sessions, lasting 5 minutes each and distributed across 5 consecutive days, caused retrograde amnesia. Indeed the Sham rats showed a significant preference (above chance; p < .05) for the novel object during the 2-minute retention test, but not the HPC rats (p > .05). In contrast, HPC-damaged rats that received 10 sample sessions, each lasting 5 minutes and distributed over 2 weeks, did not show a retrograde impairment as they investigated the novel object significantly more than the sample object (p < .05). A similar preference for the novel object (p < .05) was observed when the HPC rats received 30 sample sessions, distributed across 6 weeks, prior to surgery. Combined, these findings suggest that object recognition memory may be dependent on the HPC, but that additional learning non-HPC systems may also support the memory.