Spatial reference and working memory across the lifespan of male Fischer 344 rats

Abstract

Loss of mnemonic function is among the earliest and most disconcerting consequences of the aging process. This study was designed to provide a comprehensive profile of spatial mnemonic abilities in male Fischer 344 (F344) rats across the lifespan. Young, middle-aged, and aged F344 rats were trained in spatial reference and working memory versions of the water maze task. There was a progressive age-related decline in spatial reference memory across the lifespan. Reliable individual differences were observed among aged rats, with some aged rats performing as well as young cohorts and others performing outside this range. An age-related delay-dependent decline was observed on a working memory version of the water maze task although no relationship between performance on reference and working memory tasks was present. Notably, middle-aged rats were impaired relative to young on both tasks. Together these data demonstrate that individual differences in spatial reference memory exist among aged F344 rats and provide novel data demonstrating an unrelated decline in working memory across the lifespan, suggesting that age-related mnemonic dysfunction may occur across multiple brain systems.

Fig. 1. Spatial Reference Memory Performance of Young, Middle-aged and Aged F344 rats

Cumulative search error ± S.E. (A.) and pathlength ± S.E. (B.) across the four training trial blocks is shown for young (black circles), middle-aged (gray circles) and aged (open circles) rats. Panel (C.) shows mean search error ± S.E. on probe trials interpolated throughout the spatial learning protocol (every sixth trial). All age groups improved over the course of training although a significant interaction was observed such that aged rats did not improve their performance to the same degree as young and middle-aged rats (B, C). Fisher’s LSD post hoc comparisons indicated that middle aged rats were significantly impaired relative to young rats (A, C) and that aged rats were significantly impaired relative to both young and middle-aged rats (A–C). See text for statistical analyses.

Fig. 2. Individual Differences in Spatial Reference Memory Performance Among Young, Middle-aged, and Aged F344 Rats

Panel (A.) shows the distribution of individual Spatial Learning Indices for young (Y), middle-aged (MA), and aged (A) rats. Despite the fact that middle-aged rats were impaired relative to young rats, the majority of middle-aged rats performed within the range of young. Note the variability in performance among aged rats, however, such that some aged rats performed on par with young cohorts and others performed outside this range. Panel (B.) shows mean search error ± S.E. on probe trials for young, middle-aged, and aged rats sub-grouped into aged better-performers (those that fell within the range of young performance) and aged worse-performers (those that fell outside this range). Young, middle-aged and aged better-performers all improved to a similar degree across training, but aged worse-performers (open circles with dashed line) had a strongly attenuated learning curve.

Fig. 3. Frequency Histograms of Individual Probe Trial Performance in the Spatial Reference Memory Task for Young and Aged 344 Rats

Frequency distributions of performance on individual probe trials for young (A, C) and aged (B,D) rats are shown for probe trials early in training (probe trials 1 and 2 (A.,B.)) and late in training (probe trials 3 and 4 (C.,D.)). Both age groups show improved performance over the course of training as indicated by a leftward shift in the distribution between probe trials 1&2 and 3&4. Note that unlike training trials, in which individual trial length can be confounded by non-mnemonic variables (e.g. circling strategy and start position), only unimodal distributions are observed across ages in the probe trial analysis. These data strongly support the contention that cognitive performance is consistent across trials, even at advanced age.

Fig. 4. Spatial Working (Delayed Match-To-Place) Memory Performance of Young, Middle-aged, and Aged F344 Rats

Bar graphs show Mean Pathlength Difference ± S.E. for young (black bars), middle-aged (gray bars), and aged (open bars) rats on retention trials with varying delays. Although no differences among age groups were present with a 30 min delay, at both 2 and 6 h delays, Fisher’s LSD post hoc comparisons indicated that aged rats performed significantly worse than the middle-aged rats. Additionally, at the 2 h delay there was a trend toward aged rats performing significantly worse than young rats, a difference which became significant at the 6 h delay, at which middle-aged and young rats also differed. Note that at 6 h, the Mean Pathlength Difference for aged rats was near zero, indicating no retention of the platform location.