Neuroendocrine regulation of individual differences in social phenotype

这项计划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。裸鼹鼠提供了一个强大的机会，研究神经控制的社会表型。它们是小型啮齿动物，在哺乳动物中表现出最严格的社会和生殖等级，生活在多达300个个体的大型群体中，其中生殖仅限于一个繁殖雌性（称为女王）和一到三个繁殖雄性。繁殖者在社会上对所有其他殖民地的成员都具有支配地位，这些成员被称为下属，由于女王的存在，这些下属保持非繁殖状态。从从属到繁殖者的社会地位转变引发了他们大脑的形态和功能变化，包括控制社会行为的区域。我们发现RFamide相关肽-3（RFRP-3）是负责抑制动物的激素，但压力激素和催产素（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。目标1中的实验将通过操纵激素水平和测量大脑中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，我们将利用这样一个事实，即下属可以进一步细分为工人和士兵，尽管几乎没有人知道他们的大脑有什么不同。目标2将描述亚种姓之间的神经内分泌差异，并测试催产素在个人是否是亲社会工作者或侵略性士兵中的因果作用。最后，裸鼹鼠可以转变为任何社会表型，尽管存在特定角色的个体倾向。使用行为和机制的方法，目标3将探讨早期环境如何影响不同次种姓的发展轨迹。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，以及这些影响如何进一步受到表观遗传和环境因素的影响。通过利用裸鼹鼠显著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，以及社会环境如何影响哺乳动物大脑的发育和可塑性。

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.