Not all rat pups are treated equally: Behavioral, neural, and (epi)genetic mechanisms mediating mother-offspring dynamics

并非所有的幼鼠都受到平等对待：行为、神经和（表观）遗传机制介导母子动态

• 批准号: RGPIN-2015-05229
• 负责人: Fleming, Alison
• 金额: $ 4.15万
• 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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613428
• 关键词: rat; pups; treated; equally; Behavioral

Mothering quality relies on the integrity of multiple physiological and behavioural systems, and on early experiences that impact how a mother mothers. This proposal focuses on the dynamics of mother-pup interactions at the behavioural, neurophysiological, and (epi)genetic levels. I hypothesize that the effects of maternal care on offspring behaviour and neurophysiology depend upon individual characteristics of both mother and offspring, and the interaction between mother and offspring. Our recent NSERC-funded studies have focused on sources of inter-individual differences in mothering. Our approach has been to explore the variety of behavioural systems and their neurophysiologies that are activated in the new mother that contribute to the quality, intensity, and timing of maternal behavior with offspring, including mother’s impulsivity, attention, reward processing, and memory, which in turn are affected by mother’s own early experiences. We have also examined hormone and neurotransmitter systems involved in the regulation of mother-pup dynamics, including corticosterone, striatal dopamine, dopamine and oxytocin receptors, brain plasticity, and genetics and gene expression dopamine and serotonin systems at transcript and protein levels in relevant brain areas. However, with the exception of our most recent study, all our previous work has focused on factors that affect the mother, and we have assumed that mother responds in a uniform fashion to different offspring. The next phase of our research extends this work by focusing on factors that regulate mothers’ DIFFERENTIAL parenting towards different pups in the litter and the differences in early experiences acquired by these individual pups that leads to differences in their subsequent development. Here we also drill down on brain areas associated with mothering and the genetic and epigenetic mechanisms that account for effects of differential mothering on the development of their subsequent mothering and associated behaviors and underlying brain mechanisms; to this end we will explore both within- and between-litter interactions between mother and pups. We will use genetic analyses in dopamine systems in outbred rats combined with epigenetic analyses and studies of pup cues and maternal factors that regulate maternal attention and nurturing in the mother rat. At the neurophysiological level, we will examine relationships between dopamine single-nucleotide polymorphism genetic and DNA methylation epigenetic variations, dopamine neurotransmitter systems and mother-pup dynamics. This research program will provide an explanation of mechanisms that mediate variations in parenting and its effects on offspring (F1 generation) at multiple levels, and inform research in human development where differential and transgenerational parenting are emerging foci of interest.

母亲的质量依赖于多个生理和行为系统的完整性，以及影响母亲如何母亲的早期经验。这项建议的重点是在行为，神经生理学和（epi）遗传水平上的母子互动的动态。我假设，母亲照顾对后代的行为和神经生理学的影响取决于母亲和后代的个体特征，以及母亲和后代之间的相互作用。我们最近的NSERC资助的研究集中在母性的个体间差异的来源。我们的方法是探索各种行为系统及其神经生理学，这些系统和神经生理学在新母亲中被激活，有助于母亲与后代的行为的质量，强度和时间，包括母亲的冲动，注意力，奖励处理和记忆，这反过来又受到母亲自己的早期经历的影响。我们还研究了激素和神经递质系统参与调节母鼠的动力学，包括皮质酮，纹状体多巴胺，多巴胺和催产素受体，大脑可塑性，遗传学和基因表达多巴胺和血清素系统在转录和蛋白质水平在相关的大脑区域。然而，除了我们最近的研究之外，我们以前的所有工作都集中在影响母亲的因素上，我们假设母亲对不同的后代做出统一的反应。我们的研究的下一阶段扩展了这项工作，重点关注调节母亲对窝中不同幼崽的差异养育的因素，以及这些幼崽获得的早期经验的差异，导致其随后的发展差异。在这里，我们还深入研究了与母性相关的大脑区域以及遗传和表观遗传机制，这些机制解释了差异性母性对其随后母性发展的影响以及相关的行为和潜在的大脑机制;为此，我们将探索母亲和幼崽之间的窝内和窝间相互作用。我们将使用遗传分析在多巴胺系统在远交大鼠结合表观遗传分析和研究的小狗线索和母亲的因素，调节母亲的注意力和养育母鼠。在神经生理学水平上，我们将研究多巴胺单核苷酸多态性遗传和DNA甲基化表观遗传变异，多巴胺神经递质系统和母婴动力学之间的关系。该研究计划将提供一个解释的机制，调解父母的变化及其对后代（F1代）在多个层面上的影响，并告知人类发展的研究，其中差异和跨代养育是新兴的兴趣焦点。