The Molecular Underpinnings of Complex Social Behavior

复杂社会行为的分子基础

• 批准号: 9894918
• 负责人: Daniel Kronauer
• 金额: $ 25万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9894918
• 关键词: Affect; Ants; Behavior; Behavioral; Behavioral Assay; Behavioral Genetics; Biogenic Amines; Biological; Biological Models; Biology; Brain; CRISPR/Cas technology; Chemicals; Communication; Complex; Computer Vision Systems; Cues; DNA; DNA Methylation; Defect; Development; Disease; Environment; Epigenetic Process; Facial Expression; Genetic; Genetic study; Histones; Human; Impairment; Individuality; Insecta; Language; Light; Lobe; Mammals; Maps; Measures; Mental Depression; Modeling; Molecular; Monitor; Mood Disorders; Neurobiology; Neurodevelopmental Disorder; Neuromodulator; Neuropeptides; Organism; Performance; Pharmacology; Process; Research; Resources; Rodent; Social Behavior; Social Environment; Social Interaction; Societies; System; Transgenic Organisms; Work; autism spectrum disorder; communication behavior; fly; innovation; insight; knockout gene; neurobiological mechanism; novel; social; social cognition; social group; tool

Humans are highly social. Our brains have evolved to recognize and interpret the expression of faces and to produce and process language. Our behavior is modulated by our social interactions, and defects in social cognition manifest themselves in various disorders, including depression and autism. However, it has remained challenging to model these conditions in classic genetic systems such as rodents and flies because they only display basic social behaviors. Social insects such as ants, on the other hand, have evolved sophisticated societies and social behaviors, including nestmate recognition and complex communication via chemical cues. Their behavior is contingent on the social environment, giving rise to cooperation and division of labor. We study ants to understand the basic genetic and neurobiological mechanisms underlying these phenomena. Because most of the molecules that modulate social behavior, such as neuropeptides, biogenic amines, and epigenetic marks on DNA and histones are conserved from insects to mammals, many of the insights gained from ants will also be applicable to humans. Over the past five years we have developed tools for the clonal raider ant Ooceraea biroi, a species that combines complex social insect biology with unprecedented experimental control. We can now monitor social behavior using computer vision, measure, map, and pharmacologically manipulate candidate neuromodulators in the ant brain, and create stable gene knockout and transgenic lines using CRISPR technology. We will study the development, organization and activity of the ant antennal lobe, the part of the brain that processes the ants' sophisticated chemical language. We will also conduct a large unbiased screen to identify candidate neuromodulators that affect social behavior. We will then manipulate these candidates pharmacologically and genetically to describe their function in more detail. We will also genetically disrupt DNA methylation, a common epigenetic mark implicated in behavioral individuality and plasticity. Finally, we will study how communication and social behavior affect the performance of social groups in dynamic and challenging external environments. This work will elucidate how, on a molecular level, the brains of social partners interact. This work is innovative because it uses a novel and uniquely suited study species to take a complementary approach to important biological questions of biomedical relevance. It will produce additional tools and resources to further establish the clonal raider ant as a model system for behavioral genetics, and it will shed light on the molecular mechanisms underlying social behavior, which can then be studied further in other species including humans.

人类具有高度社会性。我们的大脑已经进化到能够识别和解释 面孔并产生和处理语言。我们的行为受到社交的调节 相互作用和社会认知缺陷表现为各种疾病，包括 抑郁症和自闭症。然而，在这些条件下建模仍然具有挑战性 经典的遗传系统，如啮齿动物和苍蝇，因为它们只表现出基本的社会性 行为。另一方面，像蚂蚁这样的社会性昆虫已经进化出了复杂的社会 和社会行为，包括同伴识别和通过化学物质进行的复杂交流 提示。他们的行为取决于社会环境，从而产生合作和 分工。我们研究蚂蚁是为了了解基本的遗传和神经生物学 这些现象背后的机制。因为大多数调节社交的分子 行为，例如神经肽、生物胺以及 DNA 和组蛋白上的表观遗传标记 从昆虫到哺乳动物都是保守的，从蚂蚁身上获得的许多见解也将被保留 适用于人类。在过去的五年里，我们为克隆袭击者蚂蚁开发了工具 Ooceraea biroi，一个将复杂的社会性昆虫生物学与前所未有的 实验控制。我们现在可以使用计算机视觉来监控社会行为、测量、 绘制蚂蚁大脑中候选神经调节剂的图谱并进行药理学操作，并创建 使用 CRISPR 技术实现稳定的基因敲除和转基因株系。我们将研究 蚂蚁触角叶的发育、组织和活动，触角叶是大脑的一部分 处理蚂蚁复杂的化学语言。我们还将进行一次大型的公正的 筛选以确定影响社会行为的候选神经调节剂。我们随后将 从药理学和遗传学上操纵这些候选者来描述它们的功能 更多细节。我们还将从基因上破坏 DNA 甲基化，这是一种常见的表观遗传标记 涉及行为个性和可塑性。最后我们要研究的是如何沟通 社会行为影响社会群体在动态和具有挑战性的外部环境中的表现 环境。这项工作将在分子水平上阐明社会伙伴的大脑如何 相互影响。这项工作具有创新性，因为它使用了一种新颖且独特的研究物种来 对生物医学相关的重要生物学问题采取补充方法。它将 制作额外的工具和资源以进一步建立克隆袭击者蚂蚁的模型 行为遗传学系统，它将揭示潜在的分子机制 社会行为，然后可以在包括人类在内的其他物种中进一步研究。