Dopaminergic plasticity underlying bonding and loss

多巴胺能可塑性是结合和损失的基础

• 批准号: 10386496
• 负责人: Anne Pierce
• 金额: $ 4.33万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-10 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386496
• 关键词: Address; Aggressive behavior; Award; Behavior; Behavioral; Behavioral Assay; Binding; Bolus Infusion; Clinical; Complex; DRD1 gene; Desire for food; Doctor of Philosophy; Dopamine; Dopamine Receptor; Ensure; Fiber; Funding; Health; Individual; Individual Differences; Kinetics; Lead; Learning; Maintenance; Measures; Mediating; Mediator of activation protein; Mental Health; Microtus; Motivation; Neurobiology; Nucleus Accumbens; Optics; Pain; Pair Bond; Partner in relationship; Personal Satisfaction; Pharmacology Study; Phase; Photometry; Psyche structure; Receptor Activation; Research; Resolution; Rewards; Role; Sample Size; Sexual Partners; Social Behavior; Social Environment; Social Functioning; Social Interaction; Social Processes; Social isolation; Source; Sum; System; Testing; Time; Training; Up-Regulation; Variant; Work; dopamine system; experience; extracellular; in vivo; individual variation; innovative neurotechnologies; insight; millisecond; novel; optogenetics; physical conditioning; prairie vole; preference; receptor expression; relating to nervous system; response; sensor; social; social attachment; social engagement; social relationships; tool

Project Summary: While strong and healthy social relationships positively contribute to our health and wellbeing, their loss is detrimental for our mental and physical health. Monogamous prairie voles (Microtus ochrogaster) provide an ideal species to examine the neurobiology of social bonding and loss. Prior work has shown that activation of dopamine (DA) receptors in the nucleus accumbens is a critical mediator of bond formation and maintenance. Specifically, DA receptor activation is essential for forming selective affiliation towards a mating partner and subsequent aggression towards non-partners, suggesting that the functional role of DA in the nucleus accumbens transitions from partner affiliation to non-partner aggression as the bond matures. Other work suggests plasticity of the accumbal DA system accompanies bonding, including changes in DA receptor expression and ex vivo DA release. However, changes in receptor expression or capacity for release do not fully explain the shift in the function of DA from partner affiliation to novel aggression. DA release and activation of receptors needs to be context specific in order to display the appropriate behavior towards the partner or novel voles. Thus, my research examines how the dopaminergic system changes as a function of bonding in loss, including changes in release between the partner and novel voles. To do so, my dissertation leverages GRABDA and fiber photometry, two tools that I developed in prairie voles, to detect in vivo DA release in behaving voles with millisecond resolution. I use these tools to investigate three ways in which social bonding and loss can cause plasticity in the DA system that mediates the transition in bonding behaviors. In Aim 1 I ask whether there are bonding induced in vivo changes in DA release capacity. My preliminary work shows that initial bond formation and bond loss decreases optogenetically evoked DA release in the nucleus accumbens. Aim 1 will determine whether my observed results are specifically due to bonding/loss from an opposite sex partner, not from other experimental conditions or general social isolation. In Aim 2, I examine how DA release elicited by unrestricted social interaction with a partner or novel vole changes during bond maturation and loss. Finally, in Aim 3, I use a social operant paradigm to distinguish DA release during the appetitive and consummatory aspects of interaction with a partner or novel across bonding and loss. In sum, this proposal uses novel behavioral and technical approaches in prairie voles to provide insights into the dopaminergic dynamics that contribute to within- individual plasticity that enables social bonding.

项目概要： 虽然牢固而健康的社会关系对我们的健康和福祉做出了积极贡献，但它们的损失 对我们的身心健康不利。一夫一妻制的草原田鼠（Microtus ochrogaster）提供了 是研究社会联系和丧失的神经生物学的理想物种。先前的工作表明，激活 伏隔核中的多巴胺 (DA) 受体是键形成和维持的关键介质。 具体而言，DA 受体激活对于形成对交配伙伴的选择性归属和 随后对非伴侣的攻击性，表明 DA 在细胞核中的功能作用 随着债券的成熟，伏隔板从伙伴关系转变为非伙伴攻击性。其他工作 表明累积 DA 系统的可塑性伴随着结合，包括 DA 受体的变化 表达和离体 DA 释放。然而，受体表达或释放能力的变化并不 充分解释了 DA 功能从伙伴关系到新颖攻击性的转变。 DA 发布和 受体的激活需要针对具体情况，以便对受体表现出适当的行为 伙伴或新颖的田鼠。因此，我的研究考察了多巴胺能系统如何随着以下因素而变化： 损失中的联系，包括伴侣和新田鼠之间释放的变化。 为此，我的论文利用了 GRABDA 和光纤光度测定法，这是我在 Prairie 开发的两种工具 田鼠，以毫秒分辨率检测行为田鼠的体内 DA 释放。我使用这些工具来调查 社会联系和丧失可以通过三种方式导致介导过渡的 DA 系统具有可塑性 在联结行为中。在目标 1 中，我询问 DA 释放是否存在键合诱导的体内变化 容量。我的初步工作表明，初始键形成和键损失在光遗传学上减少 诱发伏隔核中的 DA 释放。目标 1 将确定我观察到的结果是否 特别是由于与异性伴侣的联系/失去，而不是由于其他实验条件或 普遍的社会孤立。在目标 2 中，我研究了如何通过与不受限的社交互动来引发 DA 释放。 伴侣或新的田鼠在债券成熟和丧失过程中发生变化。最后，在目标 3 中，我使用了社交操作 区分 DA 释放的范式在与 a 交互的食欲和完成方面 跨越联系和失落的伙伴或小说。总之，该提案使用了新颖的行为和技术 草原田鼠的方法提供了对多巴胺能动力学的见解，这些动力学有助于内部- 个体的可塑性促进了社会联系。