Social Status-dependent regulation of an identified brain circuit

社会等级是所有社会动物的组织代理人。它们允许根据群体成员的统治地位和平但不平等地分配自然资源。随着社会等级的成熟，动物开始根据它们的社会等级改变它们的行为。该项目促进了对社会攻击的神经机制以及社会经验如何根据社会等级塑造动物行为的理解。使用斑马鱼作为模式生物和行为，细胞，包括电生理学和分子分析的综合方法，研究人员研究了社会经验如何根据其社会等级调节参与行为输出调制的已识别大脑中心。具体来说，研究人员研究了社会地位如何在大脑中编码，以及它调节惊吓逃避反应的机制。 斑马鱼是解决这些关键问题的理想模式生物，因为它们是高度社会化的动物，并形成稳定的主从关系，可以很容易地进行研究。此外，斑马鱼可以通过基因改造来确定控制特定运动反应的特定途径。 该项目的结果将更好地理解社会攻击背后的神经机制，以及社会信息如何在大脑中编码以改变运动活动。此外，还为不同背景的本科生提供了丰富的研究经验，并为中学生和高中生提供了科学教育活动。本项目研究了斑马鱼下丘脑多巴胺能核团之间的相互作用及其对Mauthner神经回路的调制，该神经回路是斑马鱼逃避反应的基础。Mauthner神经元是由听觉刺激激活的单对网状脊髓神经元，并支配对侧脊髓运动神经元。阈上刺激激活Mauthner神经元并导致惊吓反应。惊吓反应也倾向于来自下丘脑的下行多巴胺能（DA）调节输入。基于DA在社会攻击、动机和压力中起重要作用的证据，本项目研究了DA控制不同社会地位动物逃避行为的机制。 为此，利用分子、电生理和钙成像、组织学、遗传学、药理学和行为方法的组合。 此外，该项目还研究了核受体在调节多巴胺能活性中的作用。 下丘脑DA神经元表达核内多巴胺受体（Pgr），这是一种转录因子，调节参与激素调节的靶基因的表达。通过初步数据表明PGR对DA通路的调节作用，进行实验来阐明确定Mauthner逃逸回路下行多巴胺能输入的社会调节的潜在神经和激素信号。 总的来说，这些研究将促进对社会信息调节行为的机制的理解。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

Social hierarchies are organizing agents for all social animals. They allow the peaceful yet unequal division of natural resources based on the dominance rank of group members. As social hierarchies mature, animals begin to alter their behavior according to their social rank. This project advances understanding of the neural mechanisms that underlie social aggression and how social experience shapes animal behavior based on social rank. Using zebrafish as a model organism and an integrative approach of behavioral, cellular, including electrophysiological, and molecular analysis, the investigators study how social experience regulates identified brain centers involved in modulation of behavioral output according to their social rank. Specifically, investigators study how social status is encoded in brain and the mechanisms through which it regulates the startle escape response. Zebrafish are an ideal model organism to address these key questions because they are highly social animals and form stable dominant-subordinate relationships that can readily be investigated. Moreover, zebrafish can be modified genetically to pinpoint specific pathways that control specific motor responses. Results from this project will provide a better understanding of the neural mechanisms underlying social aggression and how social information is encoded within the brain to alter motor activity. In addition, the project provides extensive research experiences for undergraduate students from diverse backgrounds, as well as includes science educational activities for middle and high school students.This project investigates the interplay between hypothalamic dopaminergic nuclei and their modulation of the Mauthner neural circuit that underlies escape responses in zebrafish. The Mauthner neurons are a single pair of reticulospinal neurons activated by auditory stimuli and innervate contralateral spinal motor neurons. Supra-threshold stimuli activate the Mauthner neurons and leads to the startle response. The startle response is also prone to descending dopaminergic (DA) modulatory input from the hypothalamus. Building on evidence that DA plays an important role in social aggression, motivation, and stress, this project investigates the mechanisms by which DA controls escape behavior in animals of different social status. To this end, a combination of molecular, electrophysiological and calcium imaging, histological, genetic, pharmacological, and behavioral approaches are utilized. Additionally, the project examines the role of nuclear progestin receptor in regulating dopaminergic activity. Hypothalamic DA neurons express the nuclear progestin receptor (Pgr), a transcriptional factor that regulates expression of target genes involved in hormonal regulation. Prompted by preliminary data indicating a regulatory role of Pgr on DA pathways, experiments are undertaken to elucidate the underlying neural and hormonal signals that determine social regulation of the descending dopaminergic input to the Mauthner escape circuit. Collectively, the studies will advance understanding of the mechanisms that underlie modulation of behavior by social information.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.