One of the major changes in the human brain during aging is the deterioration of memory. It has been suggested that specific neurotransmitter systems, such as the cholinergic and the noradrenergic (NE), are intimately involved in memory processes, and that changes in these systems may contribute to the age-related impairment of cognitive function. Most studies of age-related alterations in the brain are performed in the intact animal. While these studies can give valuable information, they cannot distinguish between direct effects on a neuronal population, and secondary effects caused by extrinsic factors or indirectly through other neuronal populations. By placing fetal brain tissue transplants in either young or old host animals, it is possible to create """"""""young-old"""""""" chimeras in the rat host. This study is focussed on examining the neuronal plasticity of transplanted NE neurons from the locus coeruleus (LC-NE) during aging. We propose two experiments: First, transplantation of LC-hippocampal double grafts to the anterior eye chamber and, after 22 months, addition of one more hippocampal transplant. Electrophysiology and immunohistochemistry will be performed to examine the NE innervation into young and old hippocampal grafts in the triple grafts, both which are supposedly innervated by the same NE neurons from the LC graft. The second portion of the study deals with reinnervation of young or old LC-NE neurons into young or old iris transplants. Iris transplants initiate collateral sprouting of transplanted LC neurons. This strong stimulatory response will be tested against aging to investigate a possible change in NE fiber plasticity. We believe that the transplantation model described above can answer some questions concerning intrinsic vs. extrinsic factors involved in age-related changes in noradrenergic neuron plasticity. This is the short-term ,goal of these two experiments. The long-term goal is to understand the mechanisms behind cognitive defects during aging.
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