Aged rats are impaired on an attentional set-shifting task sensitive to medial frontal cortex damage in young rats

Abstract

Normal aging is associated with disruption of neural systems that subserve different aspects of cognitive function, particularly in the hippocampus and frontal cortex. Abnormalities in hippocampal function have been well investigated in rodent models of aging, but studies of frontal cortex function in aged rodents are few. We tested young (4-5 mo old) and aged (27-28 mo old) male Long-Evans rats on an attentional set-shifting task modified slightly from previous publication. After training on two problems in which the reward was consistently associated with the same stimulus dimension, and a reversal of one problem, a new problem was presented in which the reward was consistently associated with the previously irrelevant stimulus dimension (extradimensional shift [EDS]). Aged rats as a group were significantly impaired on the EDS, although some individual aged rats performed as well as young rats on this phase. In addition, some aged rats were impaired on the reversal, although a group effect did not reach significance in this phase. Impairment in neither reversal nor EDS was associated with impairments in spatial learning in the Morris water maze. Young rats with neurotoxic lesions of medial frontal cortex are also selectively impaired on the EDS. These results indicate that normal aging in rats is associated with impaired medial frontal cortex function. Furthermore, age-related declines in frontal cortex function are independent of those in hippocampal function. These results provide a possible basis for correlating age-related changes in neurobiological markers in frontal cortex with cognitive decline.

Figure 1

Acquisition of each discrimination problem in aged and young rats. Trials to criterion represent the number of trials required to meet a criterion of six consecutive correct responses, including the criterion run. Aging results in a selective impairment on extradimensional shift (EDS) learning; there was no difference between the performance of young and aged rats on any of the phases, with the exception of the EDS in which aged rats were significantly impaired. Error bars indicate standard error of mean (SEM).

Figure 2

Relationship between EDS and reversal performance in aged rats. Performance on reversal was the only phase of discrimination learning that showed a correlation with performance on EDS. The dotted lines indicate the maximum number of trials to criterion for any subject in the young group on each phase. There are substantial individual differences in EDS performance in aged rats, with some performing as well as young rats on both the EDS and reversal. It is interesting that of the rats that are impaired on the EDS, there does not appear to be an association between EDS and reversal performance.

Figure 3

Relationship between water-maze performance and set shifting in aged rats. Examination of the relationship between performance of aged rats on the water maze and EDS (A) and on the water maze and reversal (B) reveals no correlation between spatial learning and either phase of performance of the attentional set-shifting task.