There is a plethora of data suggesting that alterations in central nervous noradrenergic and cholinergic mechanisms are associated with aging. However, to a great extend, further delineation of pre-versus postsynaptic mechanisms, of intrinsic versus extrinsic determinants, and of neuronal versus non-neuronal morphological correlates is required before we can fully understand how neurotransmission is changed in the elderly. We postulate that the isolated transplant models studied here electrophysiologically, chronoamperometrically and immunocytochemically, and studied in other projects biochemically and autoradiographically, will provide the needed delineations. The experiments will be divided into seen broad groups: 1) age-related changes in noradrenergic target areas such as cerebellum and hippocampus studies using in oculo and in vitro transplant preparation, 2) age-related change in theloncus coreruleus (LC), studies using in oculo and in vitro transplant preparations, 3) age-multiple in oculo or in vitro grafts of approximately similar ages, 4) intrinsic versus extrinsic determinants of age-related changes, studies using the graft protocols, 5) plasticity of aged LC and functional properties of """"""""new"""""""" fibers derived from re-initiation of neurite outgrowth from LC grafts, 6) age-related changes in grafts of various CNS areas, induced by exposure to putative neuronotrophic factors and 7) manipulation of cholinergic input in hippocampal grafts to validate the liquid-liquid exchange probe to be developed to measure Ach overflow in vivo.
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