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.

Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age

“…Evidence of myelin loss with age in humans is further supported by diffusion tensor imaging studies which show decreases in fractional anisotropy and increased diffusivity in white matter (including the corpus callosum), which reflects a breakdown of the underlying axon structure In aging humans, smaller corpus callosum size (Ryberg et al, 2006) and reductions in fractional anisotropy have been related to poorer cognitive performance. While the aging rat does experience cognitive decline on hippocampal based tasks such as the spatial version of the Morris water maze, the eight-arm radial maze, and the Barnes circular platform task (reviewed by Rosenzweig & Barnes, 2003), and an attentional set-shifting task that requires the medial prefrontal cortex (Barense et al, 2002), the possible implications of corpus callosum size on cognitive performance in rats have not been examined. Sex differences in aged rats are largely unexplored.…”

Individual differences in neurocognitive aging of the medial temporal lobe

“…Such evidence has been garnered in the study population that has been the focus of our work; reliable individual differences in a range of aging-sensitive behavioral measures, e.g., cued reaction time and diurnal behavior, have been dissociated from cognitive decline Burwell et al 1992;Gallagher and Burwell, 1989). Even within the broad scope of cognitive abilities that are affected by aging, dissociations have been shown between functions that depend on different neural systems, e.g., medial temporal lobe and prefrontal cortex (Barense et al 2002;Glisky et al 1995;Schoenbaum et al 2002;Zyzak et al 1995). Such dissociations support the general concept of modeling the effects of aging on the brain in a system-specific manner.…”

Acute Δ9-Tetrahydrocannabinol-Induced Deficits in Reversal Learning: Neural Correlates of Affective Inflexibility

“…The habituation and testing procedures were originally adapted from Birrell and Brown (2000) and have since been detailed elsewhere (Barense et al, 2002;Fox et al, 2003;McAlonan and Brown, 2003;Tunbridge et al, 2004). Up to 48 h before testing, animals in the behavior-positive groups were habituated to the behavioral task.…”