Advances in the Study of Social Neuroendocrinology

社会神经内分泌学研究进展

• 批准号: 9353869
• 负责人: H. Elliott Albers
• 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: 2016-09-16 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9353869
• 关键词: Aggressive behavior; Alleles; Animal Model; Animals; Anxiety Disorders; Area; Argipressin; Autistic Disorder; Behavior Disorders; Behavioral; Behavioral Mechanisms; Biological Neural Networks; CRISPR/Cas technology; Communities; Complex; DNA; Data; Development; Disease; Elements; Embryo; Emotional disorder; Engineering; Epigenetic Process; Exons; Gene Targeting; Generations; Genes; Genetic; Genetic Engineering; Genetic Techniques; Genome engineering; Goals; Growth Factor; Hamsters; Hormonal; In Vitro; Inbreeding; Individual; Injectable; Injection of therapeutic agent; Knock-out; Laboratory mice; LoxP-flanked allele; Maintenance; Mediating; Mental disorders; Mesocricetus auratus; Messenger RNA; Methods; Microinjections; Modeling; Molecular; Mood Disorders; Mus; Mutagenesis; Mutation; Neurobiology; Neuroendocrinology; Neurotransmitter Receptor; Organism; Pathway interactions; Physiological Processes; Play; Positioning Attribute; Process; Production; Protocols documentation; Receptor Gene; Reporting; Research; Rodent; Rodent Model; Role; Schizophrenia; Series; Site; Social Behavior; Study models; Symptoms; System; Technology; Transgenic Organisms; V1a vasopressin receptor; Variant; arm; base; behavioral study; design; embryonic stem cell; emotional behavior; gene function; genetic approach; genetic manipulation; genome editing; mutant; neural circuit; neurobehavioral; neurogenetics; neuromechanism; neuropsychiatric disorder; neuropsychiatry; novel; offspring; overexpression; plasmid DNA; pup; receptor; relating to nervous system; repaired; response; social; social communication; social organization; tool; transcriptome; transmission process; vector

Project Summary Neuropsychiatric illnesses represent a wide range of complex emotional and behavioral disorders, but many of these are associated with maladaptive social responses. Unfortunately, we do not have a clear enough understanding of the neural mechanisms underlying these disorders or the fundamental symptoms they share. While it has become clear that there is a substantial overlap in the neural circuitry (i.e., the Social Behavior Neural Network) controlling different social and emotional behaviors, the technology to study how behavior emerges from such a complex interacting neural network has been lacking. Variation in social behavior, both across species and within individuals of given species, arises at least in part from genetic and epigenetic differences within the Social Behavior Neural Network, and we are now in a position to understand the molecular mechanisms mediating this variation. These genetic differences are expressed as variations in critical molecular elements of neural circuits such as neurotransmitters, receptors, transporters, growth factors, etc. A significant current limitation to progress in this area is that there are no well-established genome- engineering technologies for some of the best animal species for studying social behavior and organization. Among these organisms are Syrian hamsters (Mesocricetus auratus), which have proven to be an exceptionally useful rodent model for the study of social behavior and for which there is a wealth of data, much of which has been generated by the PIs, on the neurobiological and hormonal mechanisms controlling social recognition, social avoidance, aggression, and social communication. The goal of this project is to overcome this limitation by developing and implementing state of the art genome engineering technologies in the Syrian hamster model to enable molecular interrogation of how genes act within neural circuits to regulate complex social behavior. To achieve this goal, we will use genome engineering to generate transgenic and gene- targeted mutant hamsters that will be used to investigate the function of genes that have been implicated in social behavior. The generation of these transgenic and gene-targeted hamsters will be facilitated by our recently generated Syrian hamster transcriptome data, which will be used to specifically target and manipulate a variety of neurobehaviorally-relevant hamster genes. Initially, as a proof of principle, we will focus on the arginine-vasopressin V1a receptor because of the significance of this receptor in regulating a wide range of distinct social behaviors and our long-demonstrated expertise with studying this system. The successful development of transgenic and gene-targeting approaches for Syrian hamsters will provide transformative tools to the research community for exploring the neurogenetic bases of social behaviors.

项目摘要 神经精神疾病代表了一系列复杂的情绪和行为障碍，但许多 这些与适应不良的社会反应有关。不幸的是，我们没有足够明确的 了解这些疾病背后的神经机制或它们共同的基本症状。 虽然很明显，在神经回路(即，社会行为)中有大量的重叠 神经网络)控制不同的社会和情感行为，研究行为如何 从这样一个复杂的相互作用的神经网络中脱颖而出一直是欠缺的。社会行为的变化，两者都 跨物种和在特定物种的个体内，至少部分源于遗传和表观遗传 社会行为神经网络中的差异，我们现在能够理解 调节这种变异的分子机制。这些遗传差异表现为 神经回路的关键分子元素，如神经递质、受体、转运体、生长因子、 等。目前在这一领域取得进展的一个重大限制是没有成熟的基因组- 一些最好的动物物种的工程技术，用于研究社会行为和组织。 这些生物中有叙利亚仓鼠(Mesocrictus Auratus)，它已被证明是一种 对于研究社会行为来说，啮齿动物模型非常有用，而且有大量的数据， 关于控制社会的神经生物学和荷尔蒙机制 认可、社交回避、攻击性和社交沟通。这个项目的目标是克服 通过在叙利亚开发和实施最先进的基因组工程技术来限制这种限制 仓鼠模型，使分子能够询问基因如何在神经回路中发挥作用以调节复合体 社交行为。为了实现这一目标，我们将利用基因组工程来产生转基因和基因- 靶向突变仓鼠，将被用来研究已被牵连的基因的功能 社交行为。这些转基因和基因靶向仓鼠的产生将由我们的 最近生成的叙利亚仓鼠转录组数据，这些数据将被用于特定的靶向和操纵 各种与神经行为相关的仓鼠基因。首先，作为原则的证明，我们将重点放在 精氨酸加压素V1a受体，因为该受体在调节广泛的 独特的社会行为和我们在研究这一系统方面长期展示的专业知识。成功者 为叙利亚仓鼠开发转基因和基因靶向方法将提供变革性的工具 以探索社会行为的神经遗传学基础。