NEURONAL PLASTICITY AND THYROID HORMONE

拟议的研究将确定甲状腺激素在以下方面的作用： 轴突的发芽和其他回路的变化， 银化现象 该提案的提出是由于 初步实验表明，银化是 与1）视觉和嗅觉的巨大变化有关 途径，2）增加大脑血清素含量和3）增加 大脑甲状腺激素结合能力。 阴燃是甲状腺激素发挥作用的一种变态 一个重要的角色 它的特点是1）行为的变化， 2)嗅觉印记的纳塔尔流，3）一般的变化 外观和4）的变化，调节能力。 窒息特别令人感兴趣，因为它似乎是 可逆的 这项拟议中的研究是一项长期计划的一部分， 将鲑鱼作为可塑性研究的模型， 大脑的再生和老化，将包括表征 光镜、超微结构和化学变化 大脑在银化过程中 这项研究直接影响到 来理解人类大脑回路的变化， 这些数据将提供有关甲状腺功能的信息， 神经可塑性激素。 结果将进一步阐明 神经可塑性的普遍性和独特性 变化 在鲑鱼中比在其他动物中 哺乳动物的大脑，使鲑鱼成为一个理想的模型， 控制发芽。 拟议的实验将涉及三个比较 鲑鱼种群 甲状腺抑制，甲状腺素治疗，和 正常的鱼将经常采样之前，期间和之后， 变态 1)嗅觉和视网膜投射的变化 用HRP、赖氨酸钴和电子探针测定 显微技术。 2)超微结构定量研究 视顶盖将定义突触密度的变化， 突触类型 3)脑组织中儿茶酚胺和 氨基酸类神经递质采用HPLC法测定 技术. 4)5-羟色胺能和毒蕈碱胆碱能神经元 将用免疫组织化学进行表征， 放射自显影法 5)高尔基体研究将在 寻找神经元形态的变化。 6)受体结合 将在分离的细胞上测定三碘甲状腺原氨酸的动力学 核和定量放射自显影方法将用于 测量甲状腺激素受体结合能力的变化， 组织切片。

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.