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适应性 然而，调节细胞和神经递质系统的过程与精神疾病有关。 这一过程在很大程度上仍不为人所知。 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可以在社交识别任务中发出偏好信号，并且 在之前的 Conte 中心资助期间，我们表明，在同性老鼠之间的社交互动中 BLA 中的神经活动以及奖赏回路的关键组成部分伏隔核 (NAc) 变得高度 同步与显着增强的 θ-γ 交叉频率耦合 (θ-γ CFC) 相关。 类似于非人类灵长类动物（NHP）在执行社会偏好任务期间看到的情况（参见项目 4) 以及田鼠配对期间 mPFC 和 NAc 之间的关系（项目 2）。 θ-γ CFC 可能代表了整合执行、情感和奖励回路以驱动的规范机制 我们已经成功开发了一种新型的大鼠社交行为。 识别任务，它反映了项目 4 的 NHP 研究中使用的任务，通过它我们可以 直接检查两种神经递质乙酰胆碱 (ACh) 和催产素 (OT) 在调节中的作用 社会认可以及 θ-γ CFC 在从 BLA 到 NAc 的通路中具有这两种神经递质。 已被证明在调节啮齿类动物和动物的提示辨别、θ-γ CFC 和社交互动中发挥关键作用 然而，ACh 和 OT 通常是相互独立研究的。 和 OT 在 BLA 中协同作用，以促进同种人的社会认可。在这里，我们将测试 假设 BLA 中的 OT 释放通过增强 BLA 中的 ACh 释放来促进社会认可 并促进从 BLA 到 NAc 的途径中的 θ-γ CFC 为了挑战这一假设，我们将使用状态。 最先进的基因转移和基因删除技术与途径特异性病毒载体操作相结合 选择性地针对特定的神经回路，这些神经回路被认为在社交过程中调节 BLA 神经活动 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的记录 调节情感行为的神经回路的精细结构此外，项目3的研究团队。 我们预计最终将拥有成功完成拟议研究所需的所有专业知识。 在项目 3 中，我们将显着增加对两个关键之间相互作用的理解 通过更好地理解已知在社会歧视中发挥重要作用的神经递质系统。 指导亲社会行为的系统和回路我们将能够开发更有针对性的治疗方法 针对具有社会行为缺陷的共同病理学的疾病的方法。