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.

项目摘要（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的适应性 与精神疾病有关的过程。但是，调节的细胞和神经递质系统 这个过程在很大程度上是未知的。一个始终证明在调节的区域中起着关键作用 对食欲和厌恶感和/或社交刺激的行为反应是基底外侧杏仁核 （bla）。已显示在BLA中神经元的活动在社会认可任务中表明偏好，并且 在上一个孔戴中心的资金期间，我们表明在同性老鼠之间的社交互动期间 BLA中的神经活动和奖励电路的关键组成部分，伏隔核（NAC）变得高度 同步。同步与明显增强的θ-γ跨频耦合（θ-γCFC）有关 类似于在社交偏好任务执行过程中非人类隐私（NHP）中所见的类似（请参阅项目 4）在VOL中的成对键合时（项目2）之间的MPFC和NAC之间。这些数据一起表明 θ-γCFC可能代表了整合行政，情绪和奖励电路以驱动的规范机制 社交互动过程中适当的行为反应。我们已经成功地建立了一个新颖的老鼠社交 识别任务，反映了项目4的NHP研究中使用的任务，我们可以使用它 直接检查两个神经递质乙酰胆碱（ACH）和催产素（OT）在调节中的作用 从BLA到NAC的途径中的社会识别以及θ-γCFC。这两个神经递质有 被证明在调节提示歧视，θ-γcfc和啮齿动物的社交互动中起着关键作用 NHP。但是，ACH和OT通常彼此独立研究。正是我们的内容 OT在BLA中协同行动，以促进社会认可。在这里，我们将测试 OT在BLA中释放的假设是通过增强BLA中的ACH释放来促进社会认可的假设 并在从BLA到NAC的途径中促进θ-γCFC。为了挑战这一假设，我们将使用 ART基因转移和基因缺失技术与途径特异性病毒载体操作结合 有选择地靶向特定的神经元电路，这些电路被认为可以调节社交期间的BLA神经活动 认可和歧视。项目3的PI是Amygdala领域的国际认可的专家 解剖学和生理学，并具有使用最先进的病毒载体操纵的记录 调节情感行为的神经元电路的精细结构。此外，项目3的研究团队 拥有所有必要的专业知识，以成功完成拟议的研究。我们预料到最后 在项目3中，我们将明显增加对两个关键之间相互作用的理解 已知在社会歧视中起主要作用的神经递质系统。通过更好的理解 指导亲社会行为的系统和电路我们将能够开发更多针对性的治疗 共享社会行为定义常见病理的疾病方法。