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

当你成为父母时，你的行为会发生重要的变化。对于表现出父母关怀的动物来说，成功地养育后代包括从攻击性和性行为转变为更关心和养育的行为。然而，目前尚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里，了解环境如何影响大脑，以及大脑如何影响向父母照顾的行为转变，将有助于了解环境的变化如何最终影响所有生物体的繁殖。Calisi-Rodríguez和MacManes博士之间的跨学科合作中，他们将描述基因表达和生殖所必需的重要组织中特定蛋白质水平的变化，即下丘脑，垂体和性腺，在岩鸽（Columba livia）过渡到父母照顾行为期间。像大多数鸟类一样，岩鸠孵蛋，但也是独一无二的，因为它们“哺乳”来喂养它们的幼崽，表现出刻板的鸟类和哺乳动物父母的行为。这使得鸽子成为一个潜在的强有力的理论桥梁，以了解神经生物学的过渡到养育子女。Calisi-Rodríguez和MacManes博士将生成一个大型基因组数据集，并确定参与父母护理重要阶段的关键基因。这些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的管理，并为亲子关系中的神经缺陷研究提供信息。此外，研究人员还将开发和举办年度暑期项目“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。在这两个Calisi-Rodríguez和MacManes实验室的学生将有助于作为夏季城市科学的导师和讲师，以增加有关各方的培训范围。该计划的总体目标是扩大对科学的参与，创造一个更有效率和多样化的劳动力队伍。以前的研究已经牵连到特定的激素，在维持父母照顾行为的脊椎动物，包括催产素和血管加压素（鸟类同系物：中催产素和血管催产素），血管活性肠肽和催乳素。然而，很少有人知道什么时候以及如何在任何脊椎动物的大脑过渡到父母的照顾行为，这方面的知识是从根本上了解介导父母照顾的机制是非常重要的。主要研究者，在她担任NSF博士后研究员期间，发现下丘脑神经激素，促性腺激素抑制激素（GnIH），在过渡到父母照顾的过程中，在鸟类和哺乳动物中引起含有GnIH的细胞丰度的显着变化。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在向父母照顾行为过渡期间的作用。除了这种有针对性的方法之外，他们还提出了一种强大的非靶向方法，以探索在这种转变过程中大脑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的遗传和特异性蛋白质组学变化，沿着它们与GnIH的关系，这些变化发生在向父母照顾过渡的过程中。该项目将建立在以前的工作，收集的数据将产生最完整的表征和了解迄今为止在任何脊椎动物过渡到父母照顾期间报告的神经转录和翻译的变化。所有数据和计算机代码将在已建立的储存库中公开提供，并与科学界共享。

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.