AGE-RELATED CHANGES IN THE LIMBIC SYSTEM OF THE PRIMATE BRAIN

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This project is a modification of Project 3 from the previous submission which focuses on age-related changes in the morphological and neurochemical state of the basal forebrain and temporal lobe limbic system of the primate brain. The present project has been expanded to include additional chemical neuroanatomical techniques to address age-related changes in cell number, afferent innervation and, density of high affinity uptakes sites and pre- and postsynaptic receptors of all of the major neurochemical innervation rather than cell loss form the structural and chemical substrates of age-related cognitive decline including memory impairment. This hypothesis will be investigated by addressing the following specific aims concerning age-related changes in the temporal lobe limbic system: (1) to determine if there is a selective loss in intrinsic or extent of cell death or shrinkage, (2) to determine if there is a selective loss in intrinsic or extrinsic GABAergic neurons, (3) to determine if there are alterations in the neuropil, (4) to determine whether there is a loss or altered morphology of synapses, (5) to determine if there are alterations in the density and distribution of high affinity neurotransmitter uptake sites, (6) to determine whether there are alterations in the density and distribution of pre- and postsynaptic receptors, (7) to determine whether the time course and features of the loss of magnocellular neurons of the basal forebrain. Furthermore, in collaboration with Projects 2 and 3, another aim will be to determine the age-related changes in the density and distribution of high affinity uptake sites and pre- and postsynaptic receptors in the dorsolateral prefrontal association cortex, and in collaboration with Project 5, to determine changes in these same neurotransmitter levels. To accomplish these specific aims, a combination of light and electronmicroscopic measures and state-of-the-art in vitro ligand binding techniques will be utilized. In this way, within the same animal the age-related structural and chemical neuroanatomical changes that occur in the basal forebrain and temporal lobe limbic system can be correlated with memory impairments and other cognitive dysfunctions.