The mouse attentional-set-shifting task: a method for assaying successful cognitive aging?

Abstract

Humans exhibit considerable variance in cognitive decline with age, with some exhibiting little disruption and others becoming significantly impaired. In aged rodents, individual differences in spatial memory have been used to identify putative compensatory mechanisms underlying successful hippocampal aging. However, there are few parallel rodent models of cognitive decline in frontal-cortex-mediated functions. We tested the hypothesis that, like aged humans, aged mice would exhibit greater variance in executive function measures, as compared with young mice. We examined the performance of young and aged C57BL/6N mice in the attentional-set-shifting task. Whereas young and old mice did not differ on trials-to-criterion performance, aged mice exhibited significantly greater variance in mean correct latency-selective to the extradimensional shifting stage-as compared with their younger counterparts. Thus, this task may be used to identify mechanisms underlying individual differences in decline of frontal-mediated performances with age.

Figure 1

Trials to criterion for each stage of the Attentional Set-Shifting Task (ASST) in young and old mice. Mice could perform the ASST when using odors and platforms as the perceptual dimensions. The mice were required to perform six consecutively correct responses in each stage before moving onto the next stage, from simple discrimination (SD), to compound discrimination (CD), CD reversal (CDR), intradimensional (ID) shift, ID reversal (IDR), extradimensional (ED) shift, and finally ED reversal (EDR). Data presented as mean + s.e.m., * indicates p<0.05.

Figure 2

Mean correct latency performances of mice during intradimensional (ID) and extradimensional (ED) shifts by starting dimension The mean correct latency differences of mice were measured when switching from odor (O) to platform (P) or P to O between ID and ED shifts, respectively. Irrespective of initial starting dimension (O or P), mice took significantly longer to choose the correct bowls when switching to the novel stimulus dimension. Data presented as mean + s.e.m.,* denotes p<0.05 when compared to ID shift in corresponding starting dimension.

Figure 3

Age-related differences in mean correct latency of mice moving through attentional set-shifting task (ASST) stages The mean correct latencies of young and old mice were compared as they performed the intradimensional (ID) shift, ID reversal (IDR), and the extradimensional (ED) shift. Age did not affect ID or IDR correct latencies, but negatively impacted the latency for mice to complete a correct ED shift. Data presented as mean + s.e.m., * denotes p<0.05 when compared to performance at ID shift, # denotes p<0.05 when compared to young mice.

Figure 4

Individual mean correct latency of mice at ID and ED shifts The mean correct latency of individual mice at the intradimensional (ID) and extradimensional (ED; B) shift stages were plotted and compared. Latencies to perform ID shifts did not differ by age (A). Latencies to perform ED shifts did however separate by age with some old mice (age unimpaired) exhibiting performance at comparable levels to young mice, while others mice exhibited an age-related decline in performance (age impaired) as measured by increased mean correct latency (B). * denotes p<0.05 for test of equality of error variance compared to young mice.

Figure 5

Examination of the relationship between ED shift trials to criteria and mean correct latency in young and old mice The ED shift performance of old and young (Yng) mice as measured by trials to criterion were split within the two age groups into high (poor performers) and low (good performers) quartiles (i.e. top and bottom 25%). The mean correct latencies (MCL) of these mice were then compared between quartiles within each age group. Top performing young mice as measured by ED trials to criteria did not differ significantly in speed from poorer performing mice (A). Older mice that performed well in ED shift trials to criteria were significantly slower than poorly performing older mice (B). Data presented as mean ± s.e.m. * denotes p<0.05 when compared to poor performing old mice.