Neuroendocrine regulation of individual differences in social phenotype

社会表型个体差异的神经内分泌调节

• 批准号: RGPIN-2018-04780
• 负责人: Holmes, Melissa
• 金额: $ 4.01万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=713214
• 关键词: Neuroendocrine; regulation; individual; differences; social

The overarching objective of this proposal is to understand how neuroendocrine circuits regulate stable individual differences in social behaviour. Naked mole-rats provide a powerful opportunity to study neural control of social phenotype. They are small rodents that exhibit the most rigidly organized social and reproductive hierarchy among mammals, living in large colonies of up to 300 individuals in which reproduction is restricted to a single breeding female (called the queen) and one to three breeding males. Breeders are socially dominant over all other members of the colony, called subordinates, which are kept non-reproductive by the presence of the queen. A transition in social status from subordinate to breeder triggers morphological and functional changes in their brains, including regions that control social behaviours. We have discovered that RFamide-related peptide-3 (RFRP-3) is the hormone responsible for keeping animals suppressed but that stress hormones and oxytocin, a hormone involved in social behaviour, also differ between subordinate and breeding animals. The experiments in Aim 1 will identify interactions between RFRP-3, stress hormones, and oxytocin by manipulating hormone levels and measuring changes in behaviour and gene expression in brain. Next, we will capitalize on the fact that subordinates can be further sub-divided into workers and soldiers though almost nothing is known about how their brains differ. Aim 2 will characterize neuroendocrine differences between subcastes and test a causal role for oxytocin in whether individuals are prosocial workers or aggressive soldiers. Finally, naked mole-rats can transition to any social phenotype though individual predispositions for particular roles exist. Using both a behavioural and mechanistic approach, Aim 3 will explore how early environment influences the developmental trajectory of differing subcastes. Collectively, the work proposed herein seeks to tease apart how neuroendocrine systems interact in a bidirectional manner and how these effects are further influenced by epigenetic and environmental factors. By capitalizing on the remarkable sociality of naked mole-rats to reveal how neuroendocrine systems are involved in social phenotype, this work will help reveal how specialized neural circuits control the expression of social behaviours in mammals and, in turn, how the social environment affects development and plasticity in the mammalian brain.

这一建议的首要目标是了解神经内分泌回路如何调节社会行为中稳定的个体差异。裸鼹鼠为研究社会表型的神经控制提供了一个强有力的机会。它们是一种小型啮齿动物，在哺乳动物中表现出最严格的社会组织和生殖等级制度，生活在多达300只个体的大群体中，繁殖仅限于一只繁殖雌性（称为女王）和一到三只繁殖雄性。繁殖者在社会上统治着群体中的所有其他成员，这些成员被称为下属，因为女王的存在而保持不繁殖。社会地位从从属到繁殖者的转变会引发大脑的形态和功能变化，包括控制社会行为的区域。我们已经发现，rfamily相关肽-3 （RFRP-3）是负责使动物保持压抑的激素，但应激激素和催产素（一种参与社会行为的激素）在从属动物和繁殖动物之间也有所不同。Aim 1的实验将通过控制激素水平和测量大脑行为和基因表达的变化来确定RFRP-3、应激激素和催产素之间的相互作用。接下来，我们将利用下属可以进一步细分为工人和士兵的事实，尽管几乎没有人知道他们的大脑有什么不同。目的2将描述亚种姓之间的神经内分泌差异，并测试催产素在个体是亲社会工作者还是好斗的士兵中的因果作用。最后，裸鼹鼠可以转变为任何社会表型，尽管个体倾向于特定的角色存在。使用行为学和机械学方法，Aim 3将探索早期环境如何影响不同亚种的发育轨迹。总的来说，本文提出的工作旨在梳理神经内分泌系统如何以双向方式相互作用，以及这些作用如何受到表观遗传和环境因素的进一步影响。通过利用裸鼹鼠非凡的社会性来揭示神经内分泌系统如何参与社会表型，这项工作将有助于揭示专门的神经回路如何控制哺乳动物社会行为的表达，进而揭示社会环境如何影响哺乳动物大脑的发育和可塑性。