Collaborative Research: RUI: The Neural Basis of Becoming a Parent: From Genotype to Phenotype

合作研究：RUI：成为父母的神经基础：从基因型到表型

• 批准号: 1455957
• 负责人: Rae Silver
• 金额: $ 56万
• 依托单位: Barnard College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455957&HistoricalAwards=false
• 关键词: Collaborative; Research; RUI; Neural; Basis

Important changes in behavior occur with the transition to parenthood. For animals that exhibit parental care, raising offspring successfully involves transitioning from aggressive and sexual behaviors to more caring and nurturing ones. However, it is not clear how the brain brings about this transition. In a rapidly changing world, understanding how the environment affects the brain and how the brain affects the behavioral transition into parental care will shed light on how changes in environment can ultimately affect how all organisms reproduce. In an interdisciplinary collaboration between Drs. Calisi-Rodríguez and MacManes they will characterize changes in gene expression and specific protein levels in important tissues essential for reproduction, namely the hypothalamus, pituitary, and gonads, in the rock dove (Columba livia) during the transition into parental care behaviors. Like most birds, rock doves incubate eggs, but are also unique in that they "lactate" to feed their young, showing stereotypical avian and mammalian parental behaviors. This makes doves a potentially powerful theoretical bridge to understand the neurobiology of transitions into parenting. Drs. Calisi-Rodríguez and MacManes will generate a large genomic dataset and identify critical genes involved in important stages of parental care. The results will have broad potential applications including the management of captive breeding for conservation or agricultural purposes, and to inform the study of neural deficiencies in parent-offspring bonding. In addition, the researchers will develop and host an annual summer program, "Summer City Science", to expose high school students from low-income neighborhoods and underrepresented backgrounds who excel in the sciences to a range of scientific fields. This will provide students the opportunity to work closely and personally with faculty, and their research and labs. Students in both the Calisi-Rodríguez and MacManes labs will help to serve as mentors and instructors for Summer City Science to increase the scope of the training of all parties involved. The overall wider objective of this program is to broaden participation in science, creating a more efficient and diverse workforce.Previous research has implicated specific hormones that play a role in the maintenance of parental care behavior in vertebrates, including oxytocin and vasopressin (avian homologs: mesotocin and vasotocin), vasoactive intestinal peptide, and prolactin. However, very little is known about when and how the brain transitions into parental care behavior in any vertebrate, and this knowledge is fundamentally important to understand the mechanisms that mediate parental care. The Principal Investigator, during her tenure as an NSF Postdoctoral Fellow, discovered that the hypothalamic neurohormone, gonadotropin inhibitory hormone (GnIH), caused significant changes in abundance of GnIH containing cells in both birds and mammals during the transition to parental care. Here, the researchers propose to expand this knowledge using classic offspring removal and replacement manipulations to uncover the role of GnIH during the transition to parental care behavior. In addition to this targeted approach, they propose a powerful untargeted approach to explore what other changes in the brain may be occurring during this transition. They will use high-throughput sequencing technology and immunohistochemistry to uncover all genetic and specific proteomic changes in the brain, along with their relationship to GnIH, which occur during the transition to parental care. This project will build on previous work, and the data gathered will yield the most complete characterization and understanding of changes in neural transcription and translation reported to date in any vertebrate during the transition to parental care. All data and computer code will be made publicly available in established repositories and shared with the scientific community.

在为人父母的过程中，行为会发生重大变化。对于表现出亲代关爱的动物来说，成功地养育后代需要从攻击性和性行为转变为更关心和养育的行为。然而，目前还不清楚大脑是如何实现这种转变的。在一个快速变化的世界中，了解环境如何影响大脑，以及大脑如何影响向亲代抚育的行为转变，将有助于揭示环境变化最终如何影响所有生物的繁殖方式。在一项跨学科的合作中。Calisi-Rodríguez和MacManes，他们将描述岩鸽（Columba livia）在向亲代照顾行为过渡期间，生殖所必需的重要组织，即下丘脑、垂体和性腺中基因表达和特定蛋白质水平的变化。像大多数鸟类一样，岩鸽也会孵蛋，但它们的独特之处在于，它们会“分泌乳汁”来喂养幼鸟，表现出鸟类和哺乳动物的典型育儿行为。这使得鸽子成为一个潜在的强大的理论桥梁，来理解从神经生物学到养育子女的转变。Drs。Calisi-Rodríguez和MacManes将生成一个庞大的基因组数据集，并识别涉及亲代抚育重要阶段的关键基因。该结果将具有广泛的潜在应用，包括用于保护或农业目的的圈养繁殖管理，以及为研究亲子结合的神经缺陷提供信息。此外，研究人员还将开发并主持一个年度暑期项目“夏季城市科学”，让来自低收入社区和在科学领域表现出色的背景不足的高中生接触一系列科学领域。这将为学生提供与教师及其研究和实验室密切合作的机会。Calisi-Rodríguez和MacManes实验室的学生将帮助担任夏城科学的导师和讲师，以扩大所有相关各方的培训范围。这个项目更广泛的总体目标是扩大对科学的参与，创造更高效、更多样化的劳动力。先前的研究表明，在脊椎动物中，特定的激素在维持亲代照顾行为中起作用，包括催产素和抗利尿激素（鸟类同源物：中催产素和血管催产素），血管活性肠肽和催乳素。然而，对于脊椎动物的大脑何时以及如何转变为亲代抚育行为，我们知之甚少，而这一知识对于理解调解亲代抚育的机制至关重要。在担任美国国家科学基金会博士后期间，首席研究员发现下丘脑神经激素，促性腺激素抑制激素（GnIH），在鸟类和哺乳动物向亲代抚育过渡期间，导致含有GnIH的细胞丰度发生显著变化。在这里，研究人员建议使用经典的后代移除和替换操作来扩展这一知识，以揭示GnIH在向亲代照顾行为过渡期间的作用。除了这种有针对性的方法，他们还提出了一种强大的无针对性的方法来探索大脑在这种转变过程中可能发生的其他变化。他们将使用高通量测序技术和免疫组织化学来揭示大脑中所有遗传和特定蛋白质组学的变化，以及它们与GnIH的关系，这些变化发生在向亲代抚育的过渡过程中。该项目将建立在先前工作的基础上，收集的数据将产生迄今为止报道的任何脊椎动物在向亲代抚育过渡期间神经转录和翻译变化的最完整的特征和理解。所有数据和计算机代码将在已建立的存储库中公开提供，并与科学界共享。