Neuroendocrine regulation of individual differences in social phenotype

这项提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个个体的大群体中，在这些群体中，繁殖仅限于一只繁殖的雌性(称为女王)和一到三只繁殖的雄性。繁殖者在社会上比殖民地的所有其他成员都占优势，这些成员被称为下级，因为女王的存在而不能繁殖。社会地位从从属到繁育的转变引发了它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)是负责使动物受到抑制的激素，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中也不同。Aim 1的实验将通过控制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，尽管几乎不知道他们的大脑有什么不同。目标2将描述不同亚种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攻击性士兵中的因果作用。最后，裸体鼹鼠可以转变为任何社会表型，尽管存在特定角色的个人倾向。利用行为学和机械论的方法，目标3将探索早期环境如何影响不同亚种姓的发展轨迹。总而言之，这里提出的工作试图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的社会行为的表达，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。

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.