NEURONAL PLASTICITY AND THYROID HORMONE

拟议的研究将确定甲状腺激素在

The proposed studies will define the role of thyroid hormone in the sprouting of axons and other circuitry changes during smoltification in coho salmon. The proposal is prompted by preliminary experiments which show that smoltification is associated with 1) dramatic changes in visual and olfactory pathways, 2) increases in brain serotonin content and 3) increases in brain thyroid hormone binding capacity. Smoltification is a metamorphosis in which thyroid hormone plays an important role. It is characterized by 1) changes in behavior, 2) olfactory imprinting on the natal stream, 3) changes in general appearance and 4) changes in osmoregulatory capacity. Smoltification is of particular interest because it appears to be reversible. The proposed research, which is part of a long range plan to develop salmon as a model for research on plasticity, regeneration, and aging of the brain, will include characterizing light microscopic, ultrastructural and chemical changes of the brain during smoltification. The research has direct implications for understanding changes in circuitry in the human brain because the data will provide information about the role of thyroid hormone in neural plasticity. The results will further elucidate what is universal in neural plasticity and what is unique. Changes in circuits are much easier to detect in salmon than any mammalian brain, making the salmon a ideal model for manipulation of sprouting. The proposed experiments will involve a comparison of three populations of salmon. Thyroid inhibited, thyroxine treated, and normal fish will be sampled frequently before, during and after metamorphosis. 1) Changes in olfactory and retinal projections will be determined with HRP, cobalt lysine and electron microscopic techniques. 2) Quantitative ultrastructural studies of the optic tectum will define changes in the synaptic densities and synaptic types. 3) Changes in brain content of catecholamine and amino acid neurotransmitters will be determined with HPLC techniques. 4) Serotonergic and muscarinic cholinergic neurons will be characterized with immunohistochemical and autoradiographic methods. 5) Golgi studies will be carried out in a search for changes in neuronal morphology. 6) Receptor binding kinetics of triiodothyronine will be determined on isolated cell nuclei and quantitative autoradiographic methods will be used to measure changes in thyroid hormone receptor binding capacity on histological sections.