Structural and functional connectivity of the social decision-making network

项目摘要/摘要 人类和无数其他物种生活在复杂的社会环境中，需要我们许多最重要的 在社会互动的背景下作出的决定。我们所有的社会关系都依赖于我们的能力 因地制宜的决定，包括与忠诚的合作伙伴、家人和朋友建立重要的联系。社交化 决策(SDM)网络假说认为，特定社会行为的表达被反映出来 通过结构网络的整体活动，而不是任何单一结构的活动。虽然SDM 网络已经从功能上被提出，大多数支持的证据都是基于结构上的 基因座之间的连通性以及对单个神经化学物质、大脑区域和神经元功能的检查 其中的机械装置。令人惊讶的是，我们对调节与情境相适应的社交网络功能知之甚少 行为。群居一夫一妻制的草原田鼠(Microtus Ochrogaster)提供了一个研究 通过对大脑的研究培养亲密关系的社会决策背后的神经机制 在与现有和潜在伴侣的互动中调节行为选择的电路。我们的长期目标是 剖析社会行为的神经回路(包括社会行为网络和边缘奖赏 系统)，定义在上下文适当和上下文不适当期间的正常和异常网络活动 并开发出改变电路动力学的精确干预工具。我们的理论 在SDM网络内的五个大脑结构中的配对结合行为中心的神经回路被证明具有 规范伙伴导向的附属行为、陌生人导向的攻击性行为的功能专业化 拒绝，或者两者兼而有之。我们的具体目标将检验以下假设：(目标1)结构和功能 大脑区域之间的连接将根据社会刺激的类型和配对结合状态而有所不同；(目标2) SDM网络中的实时记录将证明区域和区域间神经放电是不同的 在(A)从属关系与攻击性、(B)熟悉与陌生、(C)偏好与非偏好社交互动的过程中； 和(目标3)改变进入中央中枢的神经化学输入和激活来自中央中枢的选择投射将 促进整个神经网络活动的转变，并调整被认为是与背景相适应的行为。 最后，我们将了解区域和区域间活动在管理 加强或边缘化亲密社会关系的行为选择。这一贡献是重大的，因为它将 是第一个在SDM网络内自由使用这种神经活动的时间敏感测量的研究- 移动田鼠和Will将作为该神经网络如何在其他社交网络中指导决策的概念验证 影响我们最重要的社会关系的情景。拟议的研究具有创新性，因为它 采用同时快速测量和操纵SDM网络的神经活动，以更好地 解决网络连接的许多方面，并将新技术整合到VOLE研究中，这可能 作为如何将这些技术应用于其他非传统动物模型的模板。

PROJECT SUMMARY/ABSTRACT Humans and numerous other species live in complex social environments, requiring many of our most important decisions to be made in the context of social interactions. All of our social relationships rely on our ability to make context-appropriate decisions, including significant ties with committed partners, family, and friends. The social decision-making (SDM) network hypothesis suggests that the expression of a given social behavior is reflected by the overall activity of a network of structures rather than activity of any single structure. Although the SDM network has been proposed on functional grounds, most of the supportive evidence is based on structural connectivity among loci and on examining the function of individual neurochemicals, brain areas, and neuronal mechanisms therein. We know surprisingly little about network function that regulates context-appropriate social behaviors. The socially monogamous prairie vole (Microtus ochrogaster) provides an opportunity to examine the neural mechanisms underlying social decisions which foster intimate relationships through the study of brain circuits regulating behavioral choices in interactions with current and potential partners. Our long-term goals are to dissect the neurocircuitry of social behavior (including the social behavior network and mesolimbic reward system), define normal and aberrant network activity during context-appropriate and context-inappropriate behaviors, respectively, and develop precise interventional tools that change circuit dynamics. Our theoretical neurocircuit of pair bond behaviors centers in five brain structures within the SDM network demonstrated to have functional specialization in regulating partner-directed affiliative behaviors, stranger-directed aggressive rejection, or both. Our specific aims will test the following hypotheses: (AIM 1) structural and functional connectivity between brain regions will vary depending on type of social stimuli and pair bond status; (AIM 2) Real-time recording in the SDM network will demonstrate that regional and interregional neural firing is distinct during (a) affiliative vs aggressive, (b) familiar vs unfamiliar, and (c) preferred vs non-preferred social interactions; and (AIM 3) altering neurochemical inputs into and activation of select projections out of a central hub will promote shifts in activity across the neural network and adjust what is considered context-appropriate behaviors. Upon conclusion, we will understand the role of regional and interregional activity within a network which governs behavioral choices that either enhance or marginalize intimate social ties. This contribution is significant as it will be the first study to utilize such time-sensitive measurements of neural activity within the SDM network in freely- moving voles and will service as a proof-of-concept for how this neural network guides decisions in other social scenarios which impact our most important social relationships. The proposed research is innovative as it employs simultaneous fast measurement and manipulation of neural activity of the SDM network to better address many aspects of network connectivity and integrates new technologies into in vole research, which may serve as a template for how these technologies can be adapted for other non-traditional animal models.