Role of OT and Ach in enhancing social discrimination by modulating primate amygdalo-striatal networks

OT 和 Ach 通过调节灵长类杏仁核纹状体网络增强社会歧视的作用

• 批准号: 10090656
• 负责人: Katalin M Gothard
• 金额: $ 31.39万
• 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/10090656
• 关键词: Amygdaloid structure; Animals; Attention; Basal Nucleus of Meynert; Behavior; Behavioral; Brain; Characteristics; Cholinergic Agonists; Cholinergic Antagonists; Communication; Corpus striatum structure; Coupled; Coupling; Data; Discrimination; Eye; Face; Frequencies; Goals; Human; Image; Impairment; Individual; Individuation; Infusion procedures; Injections; Learning; Life; Link; Macaca; Measures; Mediating; Memory; Mental disorders; Messenger RNA; Microinjections; Modality; Modeling; Monkeys; Motivation; Neurons; Neurotransmitters; Noise; Nucleus Accumbens; Operant Conditioning; Outcome; Output; Oxytocin; Oxytocin Receptor; Performance; Pharmacology; Phase; Population; Prefrontal Cortex; Primates; Process; Rattus; Research Design; Research Domain Criteria; Rewards; Rodent; Role; Sensory; Shapes; Signal Transduction; Social Behavior; Social Conditions; Social Discrimination; Stimulus; System; Testing; Ventral Striatum; Visual; Work; adverse outcome; autism spectrum disorder; base; cholinergic; cholinergic neuron; design; experimental study; neuromechanism; neurophysiology; nonhuman primate; recruit; relating to nervous system; response; sensory stimulus; social; social cognition; social learning; synergism

PROJECT SUMMARY (Project 4, Gothard) Despite the great diversity of species-specific social behaviors, many of the fundamental building blocks of social behavior are shared across species. For example, correct identification of individuals allows animals to learn the unique rewards or adverse outcomes expected from interacting with different individuals. The sensory modalities involved in discriminating between individuals may be different across species, but the neural mechanisms of social discrimination may be shared. Oxytocin (OT) emerged recently as a universal factor that governs social behaviors in multiple mammalian species. In this project, we explore the role of OT in shaping basic neural processes during social learning in non-human primates, such as the discrimination of individuals and the associations of individuals with different levels of reward. The experiments converge on the central hypothesis that during social learning, OT enhances the functional coupling between the basolateral amygdala (BLA) and nucleus accumbens (NAc). Consequently, neurons in the BLA are expected to show greater selectivity for unique combinations of individuals and rewards, while the neural activity across populations of neurons in the amygdalo-striatal networks are expected to show higher oscillatory coherence. To test these hypotheses we designed a conditioned social discrimination task that takes advantage of the visual abilities of macaques to discriminate between individuals presented in videos. This approximates the ability of humans to become highly familiar and accurately predict the behaviors of individuals even without real-life interactions, a process that is impaired in many psychiatric disorders, including autism. As this reward-driven task has both perceptual and operant components, it is expected to involve activation of and communication between the BLA and NAc. The task, therefore, will generate brain states that are conducive to capture the neural signature of interactions in the amygdalo-striatal networks. We will measure and compare both single unit activity and local field potential in the BLA and NAc while monkeys perform the task after local BLA infusion of OT or vehicle. In the primates, OT receptors (OXTR) are synthesized in the nucleus basalis of Meynert (NBM), not in the BLA. This inspired our secondary hypothesis that the neurophysiological effects of OT in the BLA are mediated by cholinergic (Ach) mechanisms. The mechanisms are driven by OXTR signaling on NBM neurons that project to the BLA. The ACh system enhances learning and memory across species and we hypothesize that during social learning, OT amplifies ACh release in the BLA, thereby increasing salience of social stimuli. The precise contribution and the synergy between the OT and Ach systems in the BLA will be tested by neurophysiological recordings coupled with direct injections of OT and cholinergic agonist/antagonists into the BLA or NBM. This project is highly integrated with the rodent studies in Project 3, which investigates OT/ACh interactions in social discrimination conditioned by extrinsic reward by simultaneous recordings of local field potentials and units in the BLA and NAc of rats.

项目摘要（项目 4，Gothard） 尽管特定物种的社会行为存在巨大差异，但社会行为的许多基本组成部分 行为是跨物种共有的。例如，正确识别个体可以让动物学习 与不同个体互动所期望的独特奖励或不利结果。感官 不同物种之间区分个体的方式可能有所不同，但神经元 社会歧视的机制可能是共享的。催产素（OT）最近作为一种普遍因素出现， 控制多种哺乳动物的社会行为。在这个项目中，我们探讨了 OT 在塑造 非人类灵长类动物社会学习过程中的基本神经过程，例如个体的歧视 以及具有不同奖励水平的个人的关联。实验集中在中心 假设在社会学习过程中，OT 增强了基底外侧杏仁核之间的功能耦合 (BLA) 和伏隔核 (NAc)。因此，BLA 中的神经元有望表现出更大的选择性 个体和奖励的独特组合，而神经元群体之间的神经活动 杏仁核-纹状体网络预计将表现出更高的振荡一致性。为了检验这些假设，我们 设计了一项条件性社会歧视任务，利用猕猴的视觉能力 歧视视频中出现的个人。这近似于人类变得高度的能力 即使没有现实生活中的互动，也可以熟悉并准确地预测个人的行为，这个过程 许多精神疾病都受到损害，包括自闭症。由于这种奖励驱动的任务同时具有感知和 操作组件，预计涉及 BLA 和 NAc 的激活和通信。这 因此，任务将产生有利于捕获交互的神经特征的大脑状态。 杏仁核纹状体网络。我们将测量和比较单个单元的活动和局部现场潜力 BLA 和 NAc，而猴子在局部 BLA 输注 OT 或媒介物后执行任务。在灵长类动物中，OT 受体 (OXTR) 在 Meynert 基底核 (NBM) 中合成，而不是在 BLA 中合成。这启发了我们 第二个假设是 BLA 中 OT 的神经生理学效应是由胆碱能 (Ach) 介导的 机制。该机制由投射到 BLA 的 NBM 神经元上的 OXTR 信号驱动。乙酰胆碱 系统增强了跨物种的学习和记忆，我们假设在社会学习过程中，OT 放大 BLA 中乙酰胆碱的释放，从而增加社会刺激的显着性。准确的贡献和 BLA 中 OT 和 Ach 系统之间的协同作用将通过神经生理学记录进行测试 将 OT 和胆碱能激动剂/拮抗剂直接注射到 BLA 或 NBM 中。该项目具有很高的 与项目 3 中的啮齿动物研究相结合，该研究调查了社会歧视中 OT/ACh 的相互作用 通过同时记录 BLA 和 NAc 中的局部场电位和单位来获得外部奖励 老鼠。