The bonding brain: Substrates of social attachment in monogamous voles

联结脑：一夫一妻制田鼠社会依恋的基础

• 批准号: 10217963
• 负责人: Pavel Osten
• 金额: $ 66.71万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217963
• 关键词: 3-Dimensional; Adult; Affect; Anatomy; Animal Model; Animals; Anxiety; Area; Atlases; Behavior; Biology; Brain; Brain imaging; Brain region; Cognition; Collaborations; Communities; Data; Data Set; Decision Making; Development; Diabetes Mellitus; Dimensions; Discrimination; Disease; FOS gene; Female; Fruit; Growth; Happiness; Health; Heart Diseases; Human; Human Biology; Image; Immediate-Early Genes; Knowledge; Laboratories; Link; Mammals; Maps; Mental Depression; Methods; Microscopy; Microtus; Modeling; Modernization; Mus; NOR Mouse; Nature; Neurobiology; Neurons; Neuropeptides; Neurophysiology - biologic function; Neurosciences; Oxytocin; Pair Bond; Pattern; Personal Satisfaction; Play; Positioning Attribute; Predisposition; Rattus; Research; Research Personnel; Rewards; Rodent; Role; Shapes; Social Behavior; Social Environment; Structure; Synapses; System; Testing; Vasopressins; Viral; Well in self; Work; autism spectrum disorder; base; cell type; clinically significant; computational pipelines; computational platform; density; designer receptors exclusively activated by designer drugs; exhaustion; experience; experimental study; gene induction; imaging platform; long term memory; male; neural circuit; neural patterning; neuromechanism; novel; physical conditioning; prairie vole; quantitative imaging; recruit; relating to nervous system; reward circuitry; screening; selective expression; social; social attachment; social cognition; social neuroscience; social stress; therapeutic development; therapeutic target; tool

ABSTRACT Social bonds are central to our experience, shaping both our health and happiness. Few of these bonds are as important to well-being as one’s relationship with a partner. Because social bonds play such an important role in human lives, studies of neural mechanisms of adult attachments in animal models have a high translational value. Most commonly used laboratory models, however, do not form strong and enduring attachments. For this reason, the socially monogamous prairie vole, in which males and females form stable pair-bonds and raise young together, have become an increasingly important species in social neuroscience. Work on prairie voles, for example, has revealed how the neuropeptides oxytocin and vasopressin help bring about pair bonds by modulating the activity of subcortical reward regions. Although vole research has led to human studies that examine reward circuitry in the context of attachment, most work in human social neuroscience is focused on how cortical structures contribute to social cognition, an area that is understudied in animal models. Motivated by this gap between human and animal studies, we propose to develop and apply modern systems neuroscience tools for the automated and unbiased analyses of brain structure and function in the prairie vole. Our aim is to comprehensively map the diverse circuits that are modified during pair-bond formation, and to examine how these circuits are used during the expression of bonds. In Aim 1, we will develop a detailed three-dimensional prairie-vole brain atlas, and integrate it into a computational pipeline for the automated whole-brain imaging of neuronal cell types, long-range projections, and synaptic densities. We will then use these methods to map structural differences between mouse and prairie vole brains, between male and female prairie voles, and between bonded and un-bonded voles. In Aim 2, we will use our whole-brain approach to map brain immediate-early gene induction (including c-fos and alternatives) across a 24h interval of pair-bond formation. We follow this by identifying circuit activity associated with the selective recognition of a partner, or with the discrimination between a partner and stranger. These experiments will identify the substrates of bond formation, and will clarify how these brain regions interact with other circuits during the expression of selective attachment. Finally, in Aim 3, we will study how one specific cortical region, the retrosplenial cortex (RSC), contributes to the formation and expression of pair-bonds. This work follows a growing body of data implicating the RSC in long-term memory, human social cognition and prairie-vole bonding. The study will use AAV-based chemogenetic manipulations of the RSC to investigate its contribution to whole-brain activity patterns and prairie vole bonding.

摘要 社会纽带是我们生活的核心，塑造着我们的健康和幸福。这些债券中很少有 重要的是一个人与伴侣的关系。因为社会纽带扮演着如此重要的角色 在人类生活中，在动物模型中对成人依恋的神经机制的研究具有很高的翻译价值。 值然而，大多数常用的实验室模型不能形成牢固持久的依恋。为 因此，社会上一夫一妻制的草原田鼠，雄性和雌性形成稳定的配对关系， 一起抚养孩子，已经成为社会神经科学中越来越重要的物种。在草原上工作 例如，田鼠已经揭示了神经肽催产素和加压素是如何帮助产生配对键的。 通过调节皮层下奖励区域的活动。尽管对田鼠的研究导致了人类的研究， 在依恋的背景下检查奖励电路，人类社会神经科学的大多数工作都集中在 皮质结构如何影响社会认知，这是一个在动物模型中研究不足的领域。动机 通过人类和动物研究之间的差距，我们建议开发和应用现代系统， 神经科学工具，用于对草原田鼠的大脑结构和功能进行自动化和无偏见的分析。 我们的目标是全面绘制在成对键形成过程中被修改的各种电路， 检查这些电路是如何在债券的表达过程中使用。 在目标1中，我们将开发一个详细的三维草原田鼠脑图谱，并将其整合到一个 用于神经元细胞类型的自动化全脑成像的计算管道，远程投影， 和突触密度。然后，我们将使用这些方法来映射小鼠和小鼠之间的结构差异。 草原田鼠的大脑，雄性和雌性草原田鼠之间，以及结合和非结合的田鼠之间。在aim中 2，我们将使用我们的全脑方法来绘制大脑立即早期基因诱导（包括c-fos和 替代方案）跨越24小时间隔的对键形成。我们通过识别电路活动来跟踪它 与选择性地承认伴侣有关，或与伴侣和 陌生人这些实验将确定键形成的基质，并将阐明这些大脑如何形成键。 在选择性附着的表达过程中，区域与其他回路相互作用。在目标3中，我们将 研究一个特定的皮质区域，压后皮质（RSC），如何有助于形成， pair-bonds的表达。这项工作遵循了越来越多的数据，这些数据表明RSC与长期记忆有关， 人类的社会认知和草原田鼠的结合。该研究将使用基于AAV的化学遗传学操作， RSC研究其对全脑活动模式和草原田鼠结合的贡献。

项目成果

The transient joys of others-neural ensembles encode social approach in bonded voles.

他人短暂的快乐——神经系统编码了束缚田鼠的社交方式。

• DOI: 10.1073/pnas.2006307117
• 发表时间: 2020
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Phelps,StevenM;Gustison,MorganL
• 通讯作者: Gustison,MorganL

The evolution of brain structure captured in stereotyped cell count and cell type distributions.

从定型细胞计数和细胞类型分布中捕获的大脑结构的演变。

• DOI: 10.1016/j.conb.2019.12.005
• 发表时间: 2020
• 期刊: Current opinion in neurobiology
• 影响因子: 5.7
• 作者: Němec,Pavel;Osten,Pavel
• 通讯作者: Osten,Pavel

Central Control Circuit for Context-Dependent Micturition.

• DOI: 10.1016/j.cell.2016.08.073
• 发表时间: 2016-09-22
• 期刊: Cell
• 影响因子: 64.5
• 作者: Hou XH;Hyun M;Taranda J;Huang KW;Todd E;Feng D;Atwater E;Croney D;Zeidel ML;Osten P;Sabatini BL
• 通讯作者: Sabatini BL