A functional decline in the basal forebrain cholinergic (ACh) system may underly the mild/moderate changes in cognitive and memory capacity associated with normal aging.
One aim of the proposed research is to assess the effects of normal aging in laboratory rodents on the basal forebrain ACh system, with special reference to the function of septo-hippocampal ACh neurons. Our prior work, as well as the results of other studies, suggest that the complement of basal forebrain ACh neurons is largely intact in the aged rodent brain as indicated by cell number, measurement of choline acetyltransferase (ChAT) and high-affinity choline uptake (HACU) in its basal state. This provides an interesting background for our recent observation that the dynamic response of hippocampal and cortical HACU to a behavioral manipulation is blunted in the aged brain. In order to further examine this phenomenon, training procedures that are normally sensitive to ACh manipulation and hippocampal damage in young rats, and that distinguish the behavioral impairments of aged rats, i.e., spatial learning, will be used. Initially, HACU and (3H)- hemicholinium-3 binding in synaptosomal preparations will be examined as markers for ACh neurons. Each of these measures manifests rapid regulation to manipulations of ACh neuronal activity in young animals. Subsequent experiments are designed to determine the neuroanatomical distribution of training-induced regulation of (3H)-hemicholinium binding using in vitro autoradiographic techniques. Another goal of this project is assess the extent to which different behavioral/neurobiological markers of aging are intercorrelated. To this end, behavioral data will be obtained for young and aged rats on a series of behavioral tasks that are selected to assess different functions (learning and memory, motor competence, etc.). Subsequently, analysis of a variety of targeted neurobiological markers in forebrain systems (limbic/cortical and striatum) will be assessed. The results should indicate 1) whether age-related changes in different behavioral functions occur somewhat independently, 2) whether distinctive neurobiological markers coincide with different indices of functional decline in the aged animal, and 3) importantly, in the context of our interest in cognitive/memory functions, whether a limited set of those neurobiological markers that change with age are specifically associated with the decline in spatial learning capacity in aged rats.
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