ONTOGENY OF FOREBRAIN DOPAMINE RECEPTORS

在该奖项的支持下，国际和平协会将学习以下内容： D2、D3和D4多巴胺受体亚型探针杂交 结合脑组织提取的mRNA的Northern印迹分析； 免疫组织学技术识别相应的细胞群 与配体结合或探针杂交的区域；以及，详细的 对发育中的大体和微观神经解剖学的了解 人脑。这些获得的技能将用于补充 表征[~3H]-ym个体发育的正在进行的工作发现 09151-2与人胎脑组织结合的受体研究 放射自显影。PI新获得的技能将应用于 遵循使用从中央获得的组织的特定项目 华盛顿大学人类胚胎学实验室：1) 人前脑多巴胺受体的个体发育特征 用定量受体放射自显影鉴别大体和微量 特异性结合的神经解剖学分布；2)比较 细胞表面多巴胺受体的分布与细胞的分布 D2、D3和D4多巴胺受体信息的原位杂交；3) 表达多巴胺受体的细胞群的鉴定 (表型和/或信息)在早至中期的前脑 使用适当的组织学技术进行妊娠；4)澄清 下丘脑下层神经元之间的关系(由NGFR鉴定 免疫组织化学)到表达多巴胺的细胞群 受体；以及5)在试点项目中识别特定组织 被认为有先天性脑异常风险的标本与 没有这种风险的纸巾。在指导下提供的研究经验 这一奖项将使PI能够刻画“正常”的个体发育 人类前脑的多巴胺受体。

The PI will learn the following with the support of this award: in situ hybridization using probes for D2, D3 and D4 dopamine receptor subtypes in conjunction with Northern blot analysis of brain-extracted mRNA; immunohistological techniques to identify cell populations corresponding with the areas of ligand binding or probe hybridization; and, a detailed knowledge of the gross and microscopic neuroanatomy of the developing human brain. These acquired skills will be used to complement the findings of work-in-progress characterizing the ontogeny of [3H]-YM 09151-2 binding in human fetal brain tissue using receptor autoradiography. The PI's newly acquired skills will be applied to the following specific projects using tissues obtained from the Central Laboratory for Human Embryology at the University of Washington: 1) characterization of the ontogeny of dopamine receptors in human forebrain using quantitative receptor autoradiography to identify gross and micro- neuroanatomic distributions of specific binding; 2) comparison of the distribution of cell-surface dopamine receptors to the distribution of D2, D3 and D4 dopamine receptor message using in situ hybridization; 3) identification of the cell populations which express dopamine receptors (phenotype and/or message) int he forebrain during early-to-middle gestation using appropriate histological techniques; 4) clarification of the relationship of subplate neurons (identified by NGFR immunohistochemistry) to cell populations which express dopamine receptors; and 5) identification, in a pilot project, specific tissue specimens considered at risk for congenital brain anomaly to compare to tissues without such risk. The supervised research experience provided by this award will enable the PI to characterize the "normal" ontogeny of human forebrain dopamine receptors.