Silvio O. Conte Center for Oxytocin and Social Cognition

西尔维奥·孔特催产素和社会认知中心

• 批准号: 10090633
• 负责人: Larry J Young
• 金额: $ 236.65万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10090633
• 关键词: Ablation; Amygdaloid structure; Animal Model; Animals; Area; Attention; Autoradiography; Behavioral; Behavioral Paradigm; Brain; Brain region; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Communication; Communities; Consultations; Cues; DNA Sequence Alteration; Data; Development; Education; Education and Outreach; Electrophysiology (science); Elements; Emotions; Environment; Equipment; Ethics; Experimental Designs; Eye; Face; Faculty; Future; Gene Expression; Genetic; Genotype; Goals; Grant; Health Services Research; Histologic; Histology; Human; Human Resources; Immediate-Early Genes; Immunohistochemistry; Impairment; In Situ Hybridization; Infrastructure; Infusion procedures; Interdisciplinary Study; Learning; Macaca mulatta; Mental Health; Mental disorders; Microtome - medical device; Modality; Monitor; Neurobiology; Neurosciences; Nucleus Accumbens; Oxytocin; Oxytocin Receptor; Participant; Penetrance; Pharmacology; Pilot Projects; Population; Process; Program Research Project Grants; Rattus; Research; Research Domain Criteria; Research Personnel; Research Project Grants; Research Training; Rewards; Role; Schools; Scientist; Sensory; Series; Services; Signal Transduction; Site; Social Development; Social Discrimination; Social Functioning; Social Processes; Social skills development; Societies; Stimulus; Structure; System; Techniques; Testing; Therapeutic; Training; Training Activity; Training Programs; Underrepresented Minority; Visual; assay development; autism spectrum disorder; base; cholinergic; comparative; cryostat; density; fluorescence microscope; forging; gaze; high school; improved; information processing; insight; interdisciplinary approach; lectures; meetings; molecular phenotype; neural network; neuromechanism; novel strategies; optogenetics; outreach; prairie vole; programs; public education; receptor; reinforcer; relating to nervous system; response; social; social attachment; social cognition; social communication; social deficits; social engagement; social learning; social reciprocity; training opportunity; undergraduate research experience; web site

PROJECT SUMMARY The oxytocin (OT) system is perhaps the most viable neurobiological target for enhancing social cognition in psychiatric disorders with compromised social function, including autism spectrum disorder (ASD). In animals, OT enhances neural responsiveness to social cues, thereby facilitating social recognition, attachment and reward. In humans with ASD, intranasal OT enhances brain reward system responses to social stimuli, increases gaze to the eyes of others, and improves social reciprocity. The efficacy of intranasal OT as a therapy for social disorders is limited by poor penetrance into the brain. In order to inform future translational applications, our goal is to gain a better understanding of the precise mechanisms by which OT influence social information processing in the context of intrinsic or extrinsic reward. Social learning involves social information processing in the context of reward and is paramount to normative social skill development, and the role of OT in this process is a central theme of the Center. We will sustain a highly coordinated, interdisciplinary research program involving an outstanding team of investigators to test the hypothesis that OT facilitates social learning by enhancing the flow of information across neural networks involved in salience and reward. Project scientists will use cutting-edge techniques to manipulate OT signaling in specific circuits during social engagement to understand how OT influences socially relevant neural communication. Project 1 will examine the effect of pharmacologically-evoked endogenous OT release during a social encounter on a social salience brain network in monogamous prairie voles that have high or low densities of OT receptors. Project 2 will perform simultaneous electrophysiological recordings in three brain regions that process social information and reward during social bond formation in prairie voles. Optogenetic manipulations of the circuit will be used to test causal relationships between OT- dependent neural activity and social attachment. Project 3 will analyze the influence of optogenetic stimulation of OT release and targeted genetic mutations on neural communication in rats in the context of a social learning paradigm using extrinsic reinforcers. A potential interaction of OT and cholinergic systems will be examined. Project 4 will record neural activity in these same brain regions following local OT infusion in rhesus macaques while performing an extrinsic reward-based social discrimination visual task. A Bioanalytic Core will provide vital histological, genotyping and neural molecular phenotyping services for the research Projects. An Administrative Core will manage all Center related activities (seminar series, meetings, Pilot Project grants), provide statistical consultation and coordinate outreach and training activities of Center personnel by strengthening existing relationships and forging new ones with numerous organizations. As a result, the Center will create a vibrant collaborative research, training and outreach environment that will have a national impact on mental health research. The data collected by Center faculty will have important translational implications that will inform novel strategies for treating social deficits in psychiatric disorders.

项目摘要 催产素（OT）系统也许是增强社会认知的最可行的神经生物学靶标 具有损害社会功能的精神疾病，包括自闭症谱系障碍（ASD）。在动物中 OT增强了对社会线索的神经反应性，从而促进了社会认可，依恋和 报酬。在患有ASD的人类中，鼻内OT可以增强大脑奖励系统对社会刺激的反应，增加 凝视他人的眼睛，并改善社会互惠。鼻内OT作为社会疗法的功效 疾病受到大脑外渗性不佳的限制。为了告知未来的翻译应用，我们的目标 是为了更好地了解OT影响社会信息处理的确切机制 在内在或外在奖励的背景下。社会学习涉及在上下文中的社会信息处理 奖励，对规范社会技能发展至关重要，而OT在此过程中的作用是核心 中心主题。我们将维持一项高度协调的跨学科研究计划，涉及 杰出的调查人员团队测试以下假设，即通过增强流程来促进社会学习 涉及显着性和奖励的神经网络的信息。项目科学家将使用前沿 在社交参与期间，在特定电路中操纵OT信号的技术以了解如何 影响与社会相关的神经交流。项目1将检查药理学诱发的效果 在一夫一妻制的社交显着性大脑网络上，内源性OT释放 具有高密度的OT受体的田鼠。项目2将同时进行电生理学 在三个大脑区域的记录，可以处理社会信息和奖励在社会纽带形成期间的录音 草原田鼠。该电路的光遗传操作将用于测试OT-之间的因果关系 依赖的神经活动和社会依恋。项目3将分析光遗传刺激的影响 在社会学习的背景下，OT释放和针对大鼠神经传播的基因突变 使用外部增强剂的范式。将检查OT和胆碱能系统的潜在相互作用。 项目4将记录恒河猕猴的局部OT输注后，在同一大脑区域中记录神经活动 同时执行基于外部奖励的社会歧视视觉任务。生物分析核心将提供至关重要的 研究项目的组织学，基因分型和神经分子表型服务。行政 核心将管理所有相关活动（研讨会系列，会议，试点项目赠款），提供统计 通过加强现有的咨询和协调中心人员的外展和培训活动 关系并与许多组织建立新的关系。结果，中心将创造一个充满活力的 协作研究，培训和外展环境将对心理健康产生全国影响 研究。中心教师收集的数据将具有重要的翻译意义，这将为新颖 治疗精神疾病中社会缺陷的策略。