Role of OT in cortico-striatal and amygdalo-striatal facilitation of social attachment

OT 在皮质纹状体和杏仁核纹状体促进社会依恋中的作用

基本信息

批准号：
10090654
负责人：
Robert C Liu
金额：
$ 47.62万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
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/10090654
关键词：
Affect Amygdaloid structure Animal Model Area Attention Attenuated Behavior Behavioral Brain Brain region Communication Corpus striatum structure Coupling Cues Data Decision Making Electrophysiology (science)Etiology Experimental Designs Felis catus Frequencies Goals Impairment Interneurons Knowledge Lead Learning Link Medial Mediating Memory Microtus Molecular Neurobiology Neurons Nucleus Accumbens Oxytocin Oxytocin Receptor Pair Bond Partner in relationship Pathway interactions Phase Play Population Prefrontal Cortex Process Psychological reinforcement Receptor Activation Research Domain Criteria Rewards Rodent Role Sensory Signal Transduction Social Behavior Social Interaction Social Perception Social Values Study models System Testing affiliative behavior approach behavior base flexibility gain of function improved individual variation information processing loss of function neural circuit neurochemistry optogenetics prairie vole preference receptor expression relating to nervous system sensory system sex social social attachment social cognition social deficits social learning transmission process

项目摘要

PROJECT SUMMARY (Project 2, Liu) Oxytocin is important for many aspects of social cognition. However, it is far from understood how oxytocin acts in the brain to have its effects on social perception, learning and the formation of long-term attachments. The monogamous prairie vole (Microtus ochrogaster) is a premier animal model for studying mechanisms of attach- ment, and oxytocin acting in various reward-related brain regions is essential for prairie voles to form pair bonds. Yet exactly how oxytocin facilitates pair bonding by modulating the underlying neural circuitry during social inter- actions to form bonds is unknown, pointing to a gap in our knowledge linking neurochemical to neural circuit mechanisms of attachment. Our long-term goal is to elucidate how oxytocin modulates reward and sensory systems underlying social information processing and learning. We focus here on a key oxytocin receptor-rich node at the interface between these systems, the nucleus accumbens, which receives inputs from other oxytocin receptor-dense areas, the medial prefrontal cortex (Aim 1) and the basolateral amygdala (Aim 2). Our objective here is to determine whether manipulating the oxytocin system to impair or enhance pair bonding affects nucleus accumbens' functional connectivity with its mPFC and BLA inputs. Our central hypothesis is that oxytocin nor- mally acts to improve communication from reward and cue processing areas to local NAc circuits that integrate these channels of information during specific social interactions, helping to reinforce the ability of partner signals to elicit affiliative behavior. We validate this hypothesis using both loss-of-function and gain-of-function experi- mental designs, as well as optogenetics to test causality. The rationale for our proposal is that, once we know how oxytocin affects neural circuitry between brain areas to facilitate the formation of a selective attachment, we can begin to elucidate the molecular mechanisms for plasticity within these circuits.

项目摘要（项目2，刘）催产素对于社会认知的许多方面很重要。但是，远非了解催产素的作用在大脑中，对社会感知，学习和长期依恋的形成产生影响。这一夫一妻制的草原Vole（Microtus ochrogaster）是研究附着机制的主要动物模型。在各种与奖励相关的大脑区域作用的催产素对草原形成配对键是必不可少的。然而，催产素如何通过调节社会间期间的基本神经回路来促进配对键合形成纽带的动作尚不清楚，这表明我们的知识差距将神经化学与神经化学联系起来依恋机制。我们的长期目标是阐明催产素如何调节奖励和感觉社会信息处理和学习的基础系统。我们在这里专注于富含催产素受体的关键在这些系统之间的界面上的节点，伏隔核，从其他催产素接收输入受体致密区域，内侧前额叶皮层（AIM 1）和基底外侧杏仁核（AIM 2）。我们的目标这是确定操纵催产素系统以损害或增强对键的键是否会影响核 Accumbens与其MPFC和BLA输入的功能连接。我们的中心假设是催产素nor- Mally采取行动，以改善从奖励和提示处理领域到本地NAC电路的沟通这些在特定社交互动期间的信息渠道，有助于增强合作伙伴信号的能力引起从属行为。我们使用功能丧失和功能获得实验来验证这一假设心理设计以及测试因果关系的光遗传学。我们建议的理由是，一旦我们知道催产素如何影响大脑区域之间的神经回路以促进选择性附着的形成，我们可以开始阐明这些电路中可塑性的分子机制。