Faster forgetting contributes to impaired spatial memory in the PDAPP mouse: Deficit in memory retrieval associated with increased sensitivity to interference?

Abstract

Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model of Alzheimer’s disease as reported by Games and colleagues in an earlier paper). Experiment 1, using mice aged 13–16 mo, confirmed the presence of a deficit in a spatial reference memory task in the water maze by hemizygous PDAPP mice relative to littermate controls. However, after overtraining to a criterion of equivalent navigational performance, a series of memory retention tests revealed faster forgetting in the PDAPP group. Very limited retraining was sufficient to reinstate good memory in both groups, indicating that their faster forgetting may be due to retrieval failure rather than trace decay. In Experiment 2, 6-mo-old PDAPP and controls were required to learn each of a series of spatial locations to criterion with their memory assessed 10 min after learning each location. No memory deficit was apparent in the PDAPP mice initially, but a deficit built up through the series of locations suggestive of increased sensitivity to interference. Faster forgetting and increased interference may each reflect a difficulty in accessing memory traces. This interpretation of one aspect of the cognitive deficit in human mutant APP mice has parallels to deficits observed in patients with Alzheimer’s disease, further supporting the validity of transgenic models of the disease.

Onset of hippocampus‐dependent memory impairments in 5XFAD transgenic mouse model of Alzheimer's disease

“…The performance displayed by two, four, and six‐month‐old mice are presented on Figure A–F. Consequently, during the second series of experiments, the number of trials by session was reduced to 12 trials, to test possible greater between‐day forgetting as previously reported by other authors using other Alzheimer mouse models (Blanchard et al, ; Daumas et al, ). First, we started to train six‐month‐old mice (eight 5XFAD; 10 WT control mice).…”

Cross-species translation of the Morris maze for Alzheimer’s disease

“…For the trials were spaced to avoid the effects of hypothermia on performance. Spaced training enhances learning in healthy mice and humans (24,25) but likely increases the difficulty of the task for hAPP mice and MCI-AD patients due to forgetting between trials (26,27). Another possibility is species differences in incentive to complete the task.…”

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

“…Several studies have shown a reversal of short-term memory deficits in overtrained transgenic mice and an elimination of the spatial memory deficits with subsequent re-training (Daumas et al, 2008; Zhang et al, 2011). Additional evidence has demonstrated that overtraining or training to criteria minimizes memory deficits in older animals (Wallace et al, 1980; Beatty et al, 1985; Stewart et al, 1989).…”

“…Our particular RAM protocol has the added benefit of massed training trials over several days that yields a robust spatial memory. The effects of extensive training have been reported to mitigate learning and memory deficits across various paradigms (Wallace et al, 1980; Beatty et al, 1985; Stewart et al, 1989; Daumas et al, 2008; Zhang et al, 2011). Thus, we examine the degree to which overtraining on the RAM can produce a robust spatial memory capable of withstanding TBI and preserving memory function.…”