آموزش ترفندهای جدید موشهای مسن: اختلالات وابسته به سن در آموزش معکوس بویایی

Recent work suggests that normal aging may be associated with decline in different brain systems. In the present study, young and aged Long-Evans rats were tested in a spatial version of the Morris water maze dependent on medial temporal lobe function and also on an odor discrimination reversal task previously used to investigate orbitofrontal function. Aged rats acquired the odor discrimination problems normally but were impaired in acquiring subsequent reversals of the problems. A subset of the aged rats also exhibited impaired spatial learning in the water maze. There was no correlation between reversal performance and spatial learning in the aged rats, indicating that the reversal learning impairment was not related to decline in medial temporal lobe function. Instead the performance of the aged rats on the odor discrimination task resembled that of young rats with neurotoxic lesions of orbitofrontal cortex. These data indicate that rats show independent decline of different brain systems during normal aging and suggest orbitofrontal cortex as one prefrontal area where changes may be localized for further study.

The development of a rat model for the effects of aging on hippocampus and the medial temporal lobe system has provided considerable information relevant to understanding cognitive decline in normal aging. This approach has assessed medial temporal lobe function using a standardized spatial version of the Morris water maze in which performance is sensitive to hippocampal lesions in young rats. Repeated experiments have demonstrated that a proportion of aged Long-Evans rats perform poorly in this task relative to controls, exhibiting prolonged and non-spatial search strategies when required to remember the location of a submerged platform relative to distal cues placed around the perimeter of the pool [15]. By providing a standardized index of function, such testing has allowed rigorous examination of the underlying neural substrate to determine the etiology of the age-related decline in medial temporal lobe function [14] and [17]. Contrary to expectations, these studies indicate that functional decline is not the result of neuronal loss [35] and [37] but rather is associated with a complex set of alterations including changes in synaptic connectivity and function, gene expression and signal transduction [1], [6], [7], [18], [29] and [48]. These findings are correlated with deficits in spatial cognition and accompanied by changes in encoding and neural representations in the hippocampus [49] and [50].