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.

项目概要（项目4，Gothard） 尽管物种特有的社会行为有很大的多样性，但社会行为的许多基本组成部分， 行为是跨物种共享的。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回报或不利结果。感官 在不同的物种中，个体之间的差异可能是不同的，但是神经元的差异可能是不同的。 社会歧视的机制可以共享。催产素（OT）最近出现作为一个普遍的因素， 控制着多种哺乳动物的社会行为在这个项目中，我们探索OT在塑造 非人类灵长类动物在社会学习过程中的基本神经过程，如对个体的辨别 以及不同奖励水平的个体之间的联系。实验集中在中央 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)和神经核（NAc）。因此，预计BLA中的神经元将显示出更大的选择性 对于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-纹状体网络预期显示出更高的振荡相干性。为了验证这些假设，我们 设计了一个条件社会歧视任务，利用猕猴的视觉能力， 区别视频中呈现的个体。这近似于人类的能力， 熟悉并准确地预测个人的行为，即使没有现实生活中的互动，这一过程是 包括自闭症在内的许多精神疾病的损害。由于这种奖励驱动的任务既有知觉， 操作组件，预计涉及激活和BLA和NAc之间的通信。的 因此，任务将产生有助于捕捉大脑中相互作用的神经信号的大脑状态。 杏仁体-纹状体网络我们将测量和比较单个单元活动和局部场电位， BLA和NAc，而猴在局部BLA输注OT或溶媒后执行任务。在灵长类动物中，OT OXTR受体（OXTR）在Meynert基底核（NBM）中合成，而不在BLA中合成。这启发了我们的 第二个假设，即OT在BLA中的神经生理学作用是由胆碱能（Ach）介导的 机制等这些机制由投射到BLA的NBM神经元上的OXTR信号传导驱动。关联通道 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中的ACh释放，从而增加社会刺激的显著性。精确的贡献和 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/拮抗剂直接注射入BLA或NBM。该项目高度 与项目3中的啮齿动物研究相结合，该研究调查了OT/ACh在社会歧视中的相互作用 通过同时记录BLA和NAc中的局部场电位和单位，以外部奖励为条件 老鼠。