The general aim of this project is to test the hypothesis that the nervous and endocrine systems have reciprocal effects on each other during aging, possibly causing a positive feedback loop of deterioation. A chronic stress model will be used to alter brain-endocrine relations and to determine possible interactions between stress and aging. Morphological and electrophysiological measures will provide an assessment for age-related changes in the hippocampus, which is a proposed model for general changes during aging in the brain. The primary efforts will involve electro-physiological analyses using extracellular recording techniques in freely behaving animals with chronically implanted electrodes. Measures will be made of spontaneous unit activity and theta rhythm, plus input-output curves, frequency potentiation, paired-pulse facilitation and inhibition for both the population EPSP and spike. Some light and electron microscopic studies of dendritic and synaptic structure will also be performed. Morphological data will include synaptic density, dendritic spine area, etc. These changes in the brain will be correlated with numerous endocrine and neuroendocrine factors studied by other members of the program project group. Some in vitro studies with hippocampal slices will be performed to determine the effects of corticosterone (long latency) and ACTH (short latency) on the electrophysiological properties of hippocampal neurons. The experiments will address the following issues: (1) the effects of stress and aging on the neurophysiology and morphology of the hippocampus, (2) a possible correlation during aging between neurophysiological changes and modifications of neuroendocrine and endocrine systems, (3) the effects of adrenal-pituitary hormones on the electrophysiology of hippocampal neurons in vitro, and (4) long-term changes in opioids, catecholamines and glucocorticoids during chronic stress and aging and their association with electrophysiological changes in the hippocampus. All of these issues relate to the central theme of the program project - the interactions of stress and aging with brain-endocrine relations.