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.

项目总结（Gothard项目4）