AGE AND PATHOLOGY INTERACTION IN FRONTAL CORTEX FUNCTION

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The nucleus basalis magnocellularis (NBM) plays a role in cognition and has been implicated in behavioral changes associated with aging and with age-related pathology. Acetylcholine modulates cortical activity and plasticity; because the NBM is the major source of acetylcholine for frontal cortex, it is likely that the NBM, and lesions of the NBM, affect behavior through modulation of frontal cortical structure and function. Furthermore, NBM lesions superimposed on age-related neuronal changes may produce unique behavioral deficits and alterations in frontal cortex. Previous studies have shown that in the NBM system, aging produces unique morphological changes at different ages (Wellman et al., 1995), and that the plasticity of frontal cortical neurons changes with age (Wellman & Sengelaub, 1995). The proposed research will assess the neurochemical and behavioral correlates of these structural changes. Experiment 1 will assess performance of a radial maze task, which is sensitive to both aging and dysfunction of the NBM, in young adult, middle-aged, and aged rats with either excitotoxic or sham lesions of the NBM. Experiment 2 will assess the effects of NBM lesions on neurochemistry of frontal cortex in the young adult, middle-aged, and aged rats behaviorally characterized in Experiment 1. Potential alterations in the noradrenergic, GABAergic, cholinergic, and glutamatergic systems in frontal cortex will be assessed via quantitative autoradiography; in addition, correlations between these potential pharmacological changes and maze performance will be examined. Thus, these experiments will characterize neurochemical alterations in frontal cortex due to aging, neuropathology, and their interaction and will provide valuable data about neurochemical mechanisms of age- and pathology-related cognitive deficits.