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

OT 和 Ach 通过调节大鼠杏仁核纹状体网络增强社会歧视的作用

• 批准号: 10090655
• 负责人: Shannon Leigh Gourley
• 金额: $ 40.8万
• 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/10090655
• 关键词: Ablation; Acetylcholine; Affective; Amygdaloid structure; Anatomy; Attention; Basal Nucleus of Meynert; Behavior; Brain; Clustered Regularly Interspaced Short Palindromic Repeats; Communication; Corpus striatum structure; Coupling; Cues; Data; Desire for food; Discrimination; Disease; Efferent Pathways; Emotions; Fiber; Frequencies; Funding; Gene Deletion; Gene Transfer; Human; Impairment; Infusion procedures; International; Knock-out; Learning; Lesion; Light; Measures; Mental disorders; Microtus; Muscarinic Acetylcholine Receptor; Neurons; Neurotransmitters; Nucleus Accumbens; Operant Conditioning; Oxytocin; Oxytocin Receptor; Pair Bond; Pathology; Pathway interactions; Performance; Physiology; Play; Process; Protein Synthesis Inhibition; Rattus; Reporting; Research; Rewards; Rodent; Role; Same-sex; Sensory; Signal Transduction; Social Behavior; Social Discrimination; Social Interaction; Stimulus; Structure; System; Techniques; Testing; Viral Vector; Virus; behavioral response; cholinergic neuron; memory consolidation; multi-electrode arrays; neural circuit; nonhuman primate; novel; optogenetics; preference; prevent; receptor; receptor expression; relating to nervous system; reward circuitry; sensory stimulus; social; social cognition; social learning; stria terminalis; targeted treatment

Project Summary (Project 3, Rainnie) The ability to recognize the identity and intentions of others and to react accordingly is an evolutionarily adaptive process with relevance to psychiatric disorders. However, the cellular and neurotransmitter systems that regulate this process remain largely unknown. One region consistently shown to play a pivotal role in regulating the behavioral response to both appetitive and aversive sensory and/or social stimuli is the basolateral amygdala (BLA). The activity of neurons in the BLA has been shown to signal preference in a social recognition task, and in the previous Conte Center funding period we showed that during social interaction between same sex rats neural activity in the BLA and a key component of reward circuitry, the nucleus accumbens (NAc), became highly synchronized. Synchronization was associated with markedly enhanced θ-γ cross-frequency-coupling (θ-γ CFC) similar to that seen in non-human primates (NHP) during performance of a social preference task (see Project 4) and between the mPFC and NAc during pair bonding in voles (Project 2). Together, these data suggest that θ-γ CFC may represent a canonical mechanism for integrating executive, emotion, and reward circuits to drive appropriate behavioral responses during social interaction. We have successfully developed a novel rat social recognition task, which mirrors the task being utilized in the NHP studies of Project 4, and with which we can directly examine the role of two neurotransmitters, acetylcholine (ACh) and oxytocin (OT) in the modulation of social recognition as well as θ-γ CFC in the pathway from the BLA to the NAc. These two neurotransmitters have been shown to play key roles in regulating cue discrimination, θ-γ CFC, and social interaction in rodents and NHPs. However, ACh and OT are usually studied independently of one another. It is our contention that ACh and OT act synergistically in the BLA to facilitate social recognition in conspecifics. Here, we will test the hypothesis that OT release in the BLA acts to facilitate social recognition by enhancing ACh release in the BLA and promoting θ-γ CFC in the pathway from the BLA to NAc. To challenge this hypothesis we will use state-of- the-art gene transfer and gene deletion techniques in conjunction with pathway specific viral vector manipulations to selectively target specific neural circuits that are thought to regulate BLA neural activity during social recognition and discrimination. The PI of Project 3, is an internationally recognized expert in the field of amygdala anatomy and physiology and has a track record of using state-of-the-art viral vector manipulations to examine the fine structure of neural circuits that regulate affective behavior. In addition, the research team for Project 3 have all of the necessary expertise to successfully complete the proposed studies. We anticipate that at the end of Project 3 we will have markedly increased our understanding of the interaction between two critical neurotransmitter systems that are known to play a major role in social discrimination. By better understanding the systems and circuits that guide prosocial behavior we will be able to develop more targeted therapeutic approaches for disorders that share a common pathology of deficits in social behavior.

项目概要（项目3，Rainnie） 识别他人的身份和意图并做出相应反应的能力是一种进化上的适应能力， 与精神疾病相关的过程。然而，调节细胞和神经递质系统 这一过程在很大程度上仍不为人所知。有一个区域一直在调节气候变化方面发挥着关键作用， 对食欲和厌恶的感觉和/或社会刺激的行为反应是基底外侧杏仁核 （BLA）. BLA中神经元的活动已被证明是社会识别任务中的偏好信号， 在之前的康特中心资助期间，我们发现在同性老鼠之间的社会互动中， BLA中的神经活动和奖励回路的关键组成部分，丘脑核（NAc），变得高度活跃。 同步同步化与明显增强的θ-γ交叉频率耦合（θ-γ CFC）有关 类似于非人类灵长类动物（NHP）在执行社会偏好任务时的表现（见Project 4)和mPFC和NAc之间的配对过程中的田鼠（项目2）。这些数据表明， θ-γ CFC可能代表了整合执行、情绪和奖励回路以驱动 在社会交往中做出适当的行为反应。我们已经成功地开发了一种新型的老鼠社会 识别任务，它反映了项目4的NHP研究中使用的任务，我们可以 直接检查两种神经递质的作用，乙酰胆碱（ACh）和催产素（OT）在调制 社会认可以及从BLA到NAc的通路中的θ-γ CFC。这两种神经递质 在调节啮齿动物的线索辨别、θ-γ CFC和社会互动中发挥关键作用， NHP。然而，ACh和OT通常是相互独立的研究。我们认为乙酰胆碱 和OT在BLA中协同作用，以促进同种的社会认可。在这里，我们将测试 假设BLA中OT释放通过增强BLA中ACh释放而促进社会识别 促进β-γ CFC从BLA向NAc的途径。为了挑战这一假设，我们将使用... 现有技术的基因转移和基因缺失技术结合途径特异性病毒载体操作 选择性地靶向被认为在社交过程中调节BLA神经活动的特定神经回路， 承认和歧视。项目3的PI是国际公认的杏仁核领域的专家 解剖学和生理学，并拥有使用最先进的病毒载体操作来检查 调节情感行为的神经回路的精细结构。此外，项目3的研究小组 具备成功完成拟议研究所需的所有专业知识。我们预计到最后 通过项目3，我们将显著增加对两个关键因素之间相互作用的理解， 神经递质系统在社会歧视中起着重要作用。通过更好地了解 引导亲社会行为的系统和回路，我们将能够开发出更有针对性的治疗方法， 这些疾病都有一个共同的病理学，即社会行为缺陷。