This is a proposal for an Academic Research Enhancement Award (AREA)-R15. The long-term goal of the proposed studies is to understand the specific mechanisms underlying neural plasticity in the adult. The studies are to be carried out in an in vivo model of sympathetic and sensory perivascular axons associated with extracerebral blood vessels. Responses to intracerebroventricular infusions of nerve growth factor (NGF) are assessed. Attention is focused on sprouting responses and neurotransmitter levels after the NGF infusions. The pilot studies outlined in the application will investigate changes in the regulation of cerebrovascular axons by NGF during the aging process. Experiments will rigorously quantify and relate morphological changes with immunohistochemical observations and biochemical measurements. The proposed experiments would determine age-related change in: 1) the role of neuronal activity in the regulation of cerebrovascular axons; 2 the plasticity of sympathetic cerebrovascular axons; 3) the effects of long-term NGF infusion on cerebrovascular innervation.
