Social Status-dependent regulation of an identified brain circuit

社会等级制度是所有社会动物的组织代理人。它们允许根据集团成员的支配地位和平但不平等地划分自然资源。随着社会等级制度的成熟，动物开始根据它们的社会等级来改变它们的行为。这个项目促进了对社会攻击性背后的神经机制的理解，以及社会经验如何根据社会等级塑造动物的行为。研究人员以斑马鱼为模型生物，采用行为、细胞、电生理和分子分析的综合方法，研究社会经验如何根据社会等级调节参与调节行为输出的特定大脑中心。具体地说，研究人员研究了社会地位是如何在大脑中编码的，以及它通过什么机制来调节惊吓逃逸反应。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，并形成稳定的主从性关系，很容易被研究。此外，斑马鱼可以通过基因改造来精确定位控制特定运动反应的特定路径。该项目的结果将更好地理解社交攻击性背后的神经机制，以及社交信息如何在大脑中编码以改变运动活动。此外，该项目为来自不同背景的本科生提供了广泛的研究经验，并为初中生提供了科学教育活动。该项目研究了下丘脑多巴胺能核之间的相互作用及其对斑马鱼逃避反应基础的莫特纳神经回路的调制。Mauthner神经元是由听觉刺激激活的一对网状脊髓神经元，支配对侧脊髓运动神经元。阈值以上的刺激激活了毛特纳神经元，并导致惊吓反应。这种惊吓反应也容易受到下丘脑的多巴胺能(DA)调节性输入的影响。基于DA在社会攻击性、动机和压力中发挥重要作用的证据，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，综合运用了分子、电生理和钙成像、组织学、遗传学、药理学和行为学方法。此外，该项目还研究了核孕激素受体在调节多巴胺能活动中的作用。下丘脑DA神经元表达核孕激素受体(PGR)，这是一种转录因子，调节与激素调节相关的靶基因的表达。在初步数据显示PGR对DA通路的调节作用的推动下，我们进行了实验，以阐明潜在的神经和激素信号，这些信号决定了下行的多巴胺能输入到Mauthner逃逸回路的社会调节。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。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.