The Neuropeptide Architecture of Social Communication

社交沟通的神经肽结构

• 批准号: 9301653
• 负责人: Geert J. De Vries
• 金额: $ 18.94万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9301653
• 关键词: Affect; Aggressive behavior; Anatomy; Architecture; Area; Arousal; Autistic Disorder; Behavior; Brain; CASP3 gene; Cells; Communication; Data; Diffusion; Disease; Enterobacteria phage P1 Cre recombinase; Excision; Female; Fiber; Foundations; Functional disorder; Gene Expression; Genetic; Human; Injectable; Interneurons; Investigation; Label; Laboratories; Maps; Measures; Mental disorders; Motivation; Mus; Neurons; Neuropeptides; Output; Pharmacology; Play; Prevalence; Proteins; Rabies virus; Research; Rewards; Role; Sensory; Severities; Sex Characteristics; Signal Transduction; Social Behavior; Social Behavior Disorders; Social Controls; Societies; Source; Steroids; Structure; Structure of terminal stria nuclei of preoptic region; Synapses; System; Technology; Testing; Ultrasonics; Vasopressins; Vertebrates; Viral Vector; base; communication behavior; comparative; cost; experimental study; insight; interdisciplinary approach; interest; male; mouse Cre recombinase; nerve supply; neural circuit; neurochemistry; novel; relating to nervous system; sensory input; sensory system; social; social communication; social implication; tool; treatment strategy; vocalization

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 (AVP) innervation of the brain, which shows marked sex differences across many species, including humans, and which has been implicated in both aggressive and affiliation behavior. AVP fibers are prominent in most areas of the social brain and many of these originate from cells within the posterior bed nucleus of the stria terminalis (BNST). However, so far no studies have directly targeted these cells to test their role in social behavior. Here we do so using viral vector technology to test the overarching hypothesis that these BNST AVP cells promote male-typical affiliation and that they do so by receiving direct social sensory and arousal/reward-related modulatory input. We will test this hypothesis across two specific aims using a multi-disciplinary approach: (i) does removal of BNST AVP cells eliminate prosocial communication in male, but not female, mice? (ii) does viral-vector tracing of monosynaptic connections to BNST-AVP cells reveal sensory and modulatory inputs? The answer to these novel research questions will uncover a fundamental mechanism by which the brain regulates sexually-differentiated social communication, and will contribute to identifying causes of, and treatments for, disorders of social communication.

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 加压素（AVP）对大脑的神经支配，在许多人中表现出明显的性别差异 包括人类在内的物种，并且与攻击性和归属感有关 行为。 AVP 纤维在社交大脑的大部分区域都很突出，其中许多区域 起源于终纹后床核（BNST）内的细胞。然而，所以 到目前为止，还没有研究直接针对这些细胞来测试它们在社会行为中的作用。我们在这里做 因此，使用病毒载体技术来测试这些 BNST AVP 细胞的总体假设 促进男性典型的归属感，并且他们通过接受直接的社会感官和 唤醒/奖励相关的调节输入。我们将通过两个具体目标来检验这个假设 使用多学科方法：（i）去除 BNST AVP 细胞是否会消除亲社会性 雄性老鼠有交流，但雌性老鼠不行？ (ii) 单突触的病毒载体追踪 与 BNST-AVP 细胞的连接揭示了感觉和调节输入？这些问题的答案 新颖的研究问题将揭示大脑调节的基本机制 性别差异的社会沟通，并将有助于确定其原因和 社交沟通障碍的治疗。