CHARACTERIZATION OF HORMONE-CONCENTRATING NEURONS

这项建议将重点放在雌激素受体(ER)和 孕激素受体(PR)阳性神经元在母体发病中的作用 母亲的行为和伴随的神经内分泌事件 反应灵敏的雌性老鼠。具体目标I-怀孕是否会改变大脑的 视前区ER和PR的诱导对类固醇的敏感性 (POA)和边缘系统？这些变化是转录的还是 翻译水平？我们将测试是否有数量和分布 含有ER和PR的POA和边缘神经元在怀孕期间发生变化 如果每个神经元的受体蛋白或信使核糖核酸的数量发生了变化。 ER和PR抗体免疫细胞化学(ICC)或原位免疫细胞化学 与ER和PR mRNA的探针杂交(或Northern印迹)将是 使用。特定目标II-是大脑对雌激素和 孕激素通过特定的神经回路传导 母性反应的具体组成部分？做独特的传出 ER和PR神经元的投射构成了 母体反应包括对化学感觉输入的反应改变， 与筑巢和取回以及事件相关的马达组件 与护理有关，包括蹲伏、舔和释放催产素？ 这些实验将结合逆行神经解剖追踪和 ICC检测ER、PR。将特定人群的皮损 投射到不同功能区的ER和PR POA神经元改变 母性反应的具体组成部分？神经毒素将被用来 视前神经元的病变特定亚群将由它们的 独特的传出投射和/或怀孕改变了 感受器；行为损害将被测试。特定目标III-ER 神经元群体中的PR对母体反应性很重要 可能是由一些重要的生理事件引起的 发生在怀孕的自然过程中。这些实验将 测试POA的传入输入是否改变ER和PR的诱导 在怀孕期间在POA中。河豚毒素或神经递质 拮抗剂将被用来暂时消除对这些 神经元；对化学感觉输入进行损伤。免疫反应阳性 将检查受体蛋白或信使核糖核酸的含量和行为结果。

This proposal will focus on the role of estrogen receptor (ER) and progesterone receptor (PR) containing neurons in the onset of maternal behavior and the attendent neuroendocrine events in the maternally responsive female rat. Specific Aim I- Does pregnancy alter the brain's sensitivity to steroids by induction of ER and PR in the preoptic area (POA) and limbic system? Are these alterations at the transcriptional or translational level? We will test whether the number and distribution of POA and limbic neurons that contain ER and PR is altered during pregnancy and if the amount of receptor protein or mRNA per neuron is altered. Immunocytochemistry (ICC) with ER and PR antibodies or in situ hybridization (or Northern blot) with probes to ER and PR mRNA will be used. Specific Aim II- Is the brain's sensitivity to estrogen and progestin channeled through particular neural circuits that underlie specific components of maternal responsiveness? Do unique efferent projections of ER and PR neurons underlie the different components of the maternal response including altered responsivity to chemosensory inputs, the motor components related to nest building and retrieval, and events related to nursing including crouching, licking and oxytocin release? These experiments will combine retrograde neuroanatomical tracing with ICC detection of ER and PR. Will lesions of the specific populations of ER and PR POA neurons that project to different functional regions alter specific components of the maternal response? Neurotoxins will be used to lesion specific subsets of preoptic neurons that will be defined by their unique efferent projections and/or pregnancy altered concentration of receptors ; behavioral impairment will be tested. Specific Aim III- ER and PR in neuronal populations important for maternal responsiveness could be induced by a number of the important physiological events that occur during the natural course of pregnancy. These experiments will test whether the afferent input to POA alters the induction of ER and PR in the POA during pregnancy. Tetrodotoxin or neurotransmitter antagonists will be used to transiently eliminate afferent input to these neurons; lesion of the chemosensory input carried out. Immunoreactive receptor protein or mRNA content and behavioral results will be examined.