Neuropeptide receptor regulation of social communication

社会交流的神经肽受体调节

• 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
• 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

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.

摘要 社会行为和沟通障碍日益普遍，并构成了一个 给社会带来沉重负担。这些疾病在患病率上往往表现出性别差异， 表情和严肃性。对这些差异的一种解释是， 性别不同的社交大脑。在这方面特别相关的神经肽系统是 血管加压素（VP）神经支配的大脑，这表明显着的性别差异，在许多 物种，包括人类，并已被牵连在侵略性以及联系 行为事实上，大脑中VP的主要受体V1 aR现在是药物治疗的主要靶点。 治疗孤独症核心症状的药物。尽管这个系统很重要，但很少有人 研究直接评估了V1 aR信号如何、何时以及在何处影响 成年人的沟通行为。这种数据的缺乏在小鼠中尤为严重，这是一个关键。 生物医学相关物种。我们建议通过生成一个新的鼠标线来解决这个问题， 在Avpr 1a启动子（Avpr 1a-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，然后进行有针对性的 实验操纵V1 aR在外侧隔作为测试这种新的资源。作为 为了比较，我们还将测试LS中催产素受体在社会交往中的作用 使用相同的实验方法。经验证的Avpr 1a-Cre生产线的可用性将 使绘制连接结构和确定 行为/生理功能的不同V1 aR细胞群体使用现代技术。 反过来，这将揭示大脑调节社会活动的基本机制。 沟通，并将有助于确定的原因，和治疗，疾病的 男性和女性的社会交流。