CATECHOLAMINERGIC NEURON PLASTICITY IN AGED BRAIN

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The capacity for morphological and functional plasticity of catecholaminergic (CA) neurons in aged rat brain will be evaluated, using as a model system an aminergic tract which contacts and regulates target secretory neurons in the supraoptic nucleus (SON) which project to the neurohypophysis and secrete vasopressin (VP). These afferent norepinephrine (NE) containing axons will be neurosurgically severed, either near their point of termination at the SON, or near their cells of origin in the ventral mesencephalon. The lesion sites and the target nucleus, SON, will be examined for new fiber growth and CA reinnervation, which will be evaluated by microspectrofluorometric quantitation of endogenous CA histofluorescence, and biochemical measure of SON CA levels by high performance liquid chromatography. Qualitative assessment will include anterograde tract tracing. Functional restoration in the target neurons will be assessed by immunocytochemical staining of neurophysin and VP, radioimmunoassay of plasma VP, and monitoring of water balance (drinking, and urine volume and osmolality). The possible contribution of peripheral sympathetic innervation of SON vasculature to the reinnervation pattern will be tested by combining superior cervical ganglionectomy with each of the neurosurgical lesions, and evaluation by simultaneous visualization of vasculature and terminal fluorescence, as well as biochemical and microspectrofluorometric quantitation of CA in the target. Preliminary studies indicate that a considerable capacity for morphological regeneration is retained in the aged brain; the proposed project will provide a correlative anatomical and functional assessment.