Neuropeptide receptor regulation of social communication

社会交流的神经肽受体调节

基本信息

批准号：
9804998
负责人：
Geert J. De Vries
金额：
$ 7.72万
依托单位：
GEORGIA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9804998
关键词：
Ablation Acute Adult Affect Anatomy Animal Model Animals Anxiety Architecture Area Arousal Attention Autoradiography Behavior Behavioral Brain CASP3 gene Cell Death Cell Nucleus Cells Communication Complex Data Development Disease Drug Targeting Effectiveness Enterobacteria phage P1 Cre recombinase Female Foundations Functional disorder Future Generations Genomics Health Hormonal Human Incidence Injections Investigation Knockout Mice Knowledge Laboratories Lateral Mediating Mental disorders Modeling Modernization Motivation Motor Mus Neurologic Neurons Neuropeptide Receptor Neuropeptides Oxytocin Receptor Pharmacology Phenotype Physiological Play Population Prevalence Receptor Cell Receptor Signaling Reflex action Regulation Reporter Resources Rodent Role Sensory Services Severities Sex Differences Signal Transduction Social Behavior Social Behavior Disorders Social Controls Social Functioning Societies Symptoms System Techniques Testing Time Tissues Validation Variant Vasopressin Receptor Vasopressins Vertebrates Viral Vector autism spectrum disorder cell type communication behavior cost drug development experimental study genetic manipulation insight interest male mouse Cre recombinase nerve supply neurochemistry offspring promoter receptor receptor binding receptor expression receptor function relating to nervous system sex sexual dimorphism social social communication social deficits social implication standard measure tool treatment strategy vocal control

项目摘要

Abstract Disorders of social behavior and communication are increasingly prevalent and pose a substantial burden to society. These disorders often show sex differences in prevalence, expression, and severity. One explanation for these differences reflects dysfunction in the sexually different social brain. A particularly relevant neuropeptide system in this respect is the vasopressin (VP) innervation of the brain, which shows marked sex differences across many species, including humans, and has been implicated in aggressive as well as affiliation behavior. Indeed, the main receptor for VP in the brain, V1aR, is now a major target for drug development for treating core symptoms of autism. Despite the significance of this system, few studies have directly assessed how, when, and where V1aR signaling influences communication behavior in adults. This lack of data is particularly acute in mice, a key biomedically-relevant species. We propose to remedy this by generating a new mouse line that expresses cre-recombinase (Cre) under the control of the Avpr1a promoter (Avpr1a-Cre), rigorously characterizing its behavioral phenotype in both sexes, then performing a targeted experiment manipulating V1aR in the lateral septum as a test of this new resource. As a comparison, we will also test the role of the oxytocin receptor in LS on social communication using identical experimental approaches. The availability of a validated Avpr1a-Cre line will enable rapid progress in mapping the connectional architecture and determining the behavioral/physiological functions of different V1aR cell populations using modern techniques. This, in turn, will uncover a fundamental mechanism by which the brain regulates social communication, and will contribute to identifying causes of, and treatments for, disorders of social communication in both males and females.

抽象的社会行为和沟通障碍日益普遍，并构成了给社会带来沉重负担。这些疾病的患病率通常表现出性别差异，表达方式和严重程度。对这些差异的一种解释反映了性别不同的社交大脑。在这方面特别相关的神经肽系统是大脑的加压素 (VP) 神经支配，在许多人中表现出明显的性别差异包括人类在内的物种，并与攻击性和归属感有关行为。事实上，大脑中 VP 的主要受体 V1aR 现在是药物的主要靶点治疗自闭症核心症状的开发。尽管这个系统很重要，但很少有人研究直接评估了 V1aR 信号传导如何、何时、何地影响成人的沟通行为。这种数据的缺乏在小鼠中尤其严重，这是一个关键生物医学相关物种。我们建议通过生成新的鼠标线来解决这个问题在 Avpr1a 启动子 (Avpr1a-Cre) 的控制下表达 cre 重组酶 (Cre)，严格描述其在两性中的行为表型，然后执行有针对性的实验操作侧中隔中的 V1aR 作为对这种新资源的测试。作为一个相比之下，我们还将测试LS中催产素受体对社交沟通的作用使用相同的实验方法。经过验证的 Avpr1a-Cre 系的可用性将能够快速绘制连接架构并确定使用现代技术研究不同 V1aR 细胞群的行为/生理功能。反过来，这将揭示大脑调节社交的基本机制沟通，并将有助于确定疾病的原因和治疗方法男性和女性的社交沟通。