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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH039180-04A2
Application #
3377172
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1988-08-01
Project End
1991-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Arts and Sciences
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Burwell, R D; Whealin, J; Gallagher, M (1992) Effects of aging on the diurnal pattern of water intake in rats. Behav Neural Biol 58:196-203
Gallagher, M; Burwell, R D; Kodsi, M H et al. (1990) Markers for biogenic amines in the aged rat brain: relationship to decline in spatial learning ability. Neurobiol Aging 11:507-14
Gallagher, M; Burwell, R D (1989) Relationship of age-related decline across several behavioral domains. Neurobiol Aging 10:691-708
Jiang, H K; Owyang, V V; Hong, J S et al. (1989) Elevated dynorphin in the hippocampal formation of aged rats: relation to cognitive impairment on a spatial learning task. Proc Natl Acad Sci U S A 86:2948-51
Gallagher, M; Pelleymounter, M A (1988) An age-related spatial learning deficit: choline uptake distinguishes ""impaired"" and ""unimpaired"" rats. Neurobiol Aging 9:363-9
Decker, M W; Pelleymounter, M A; Gallagher, M (1988) Effects of training on a spatial memory task on high affinity choline uptake in hippocampus and cortex in young adult and aged rats. J Neurosci 8:90-9
Decker, M W; Gallagher, M (1987) Scopolamine-disruption of radial arm maze performance: modification by noradrenergic depletion. Brain Res 417:59-69
Decker, M W (1987) The effects of aging on hippocampal and cortical projections of the forebrain cholinergic system. Brain Res 434:423-38
Rapp, P R; Fanelli, R F; McGuire, M et al. (1987) Alterations in [3H]desmethylimipramine binding in the aged rat brain: an in vitro autoradiographic demonstration. Neurosci Lett 79:17-22
Rapp, P R; Rosenberg, R A; Gallagher, M (1987) An evaluation of spatial information processing in aged rats. Behav Neurosci 101:3-12

Showing the most recent 10 out of 11 publications