Neuronal mechanisms of visually-driven aggressive behavior

视觉驱动攻击行为的神经机制

• 批准号: 9978478
• 负责人: Andrés Bendesky
• 金额: $ 72.02万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978478
• 关键词: Aggressive behavior; Amygdaloid structure; Anatomy; Animals; Antibodies; Area; Attention; Behavior; Behavioral; Behavioral Paradigm; Biological Assay; Brain; Brain region; Cues; Data; Discrimination; Fishes; Foundations; Generations; Genome; Head; Homologous Gene; Human; Individual; Insecta; Measurement; Measures; Modeling; Modernization; Molecular; Monitor; Morphology; Movement; Mus; Muscle; Neurons; Neurosciences; Output; Partner in relationship; Perception; Positioning Attribute; Preparation; Primates; Process; Resolution; Resources; Retina; Rodent; Social Behavior; Social Discrimination; Stereotyping; Stimulus; Technology; Testing; Tracer; Transgenic Organisms; Vertebrates; Viral; Virus; Vision; Visual; Visual Pathways; Visual Perception; Visual attention; Zebrafish; anatomical tracing; awake; base; behavioral response; calcium indicator; computer studies; fighting; fly; genetic analysis; genome sequencing; innovation; insight; movie; neural circuit; neuronal circuitry; olfactory stimulus; response; siamese fighting fish; social; success; tool; vertebrate genome; visual stimulus

Project Summary Aggression is a fundamental social behavior. Though widespread, the stimuli that modulate aggression differ between species. Primates rely strongly on visual cues, while in rodents and insects olfactory stimuli are essential. Since mice and flies are the leading models of modern aggression studies, the mechanisms by which visual neural circuits modulate aggression remain largely unknown. Recent advances in genome sequencing, transgenic and viral technologies allow the application of genetically-encoded tools for tracing, monitoring and manipulating neural circuits to a wide variety of species. Here, we propose to develop an innovative model to uncover the circuitry underlying visually-evoked aggression. We will develop advanced tools and experimental setups to study the neuronal circuits and computations involved in visually-triggered aggression in Siamese fighting fish (Betta splendens). Betta have been selectively bred to be highly aggressive for hundreds of generations. They now have a fast, robust, and stereotyped aggression display in response to seeing another fish, and therefore present an ideal model for the proposed studies. We will first test whether visually-evoked aggression engages specific nodes in a circuit that receives visual input (Aim 1). We will identify these nodes in order to target them for analyses of neuronal activity. This will be achieved in a three step process. First we will anatomically trace vision-aggression circuits using anterograde tracers from the retina and retrograde tracers from the muscles used exclusively during aggression displays. We will then identify salient features of aggression-triggering visual cues, to develop visual stimuli that robustly elicit aggression and other stimuli that merely elicit visual attention but no aggression. Lastly, we will identify neurons active during aggression (using an antibody against pS6, a marker of neuronal activity) but not when fish see a control movie that elicits attention but not aggression. Together, this will enable us to identify the nodes involved in visually-evoked aggression, so we can target them for analyses of neuronal activity. We will then develop transgenic Betta to express genetically encoded calcium indicators in the brain to measure how visual stimuli that trigger aggression are represented and processed (Aim 2). Lastly, we will develop a head-fixed preparation to record neuronal activity in behaving fish, focusing first in the fish homolog of the mammalian amygdala (Aim 3). This large scale and cellular-level resolution approach will allow us to study the computations involved in the perception and discrimination of visual stimuli with varying aggression- inducing levels and to generate models that relate neuronal activity to behavioral output. The model developed in this application will present a unique and powerful platform to elucidate the neural circuitry underlying visually-evoked aggression, a project which we aspire to present as a subsequent TargetedBCP R01.

项目概要 攻击性是一种基本的社会行为。调节攻击性的刺激虽然广泛存在 物种之间存在差异。灵长类动物强烈依赖视觉线索，而啮齿类动物和昆虫则依赖嗅觉刺激 基本的。由于小鼠和苍蝇是现代攻击性研究的主要模型，因此其机制 哪些视觉神经回路调节攻击性仍然很大程度上未知。基因组的最新进展 测序、转基因和病毒技术允许应用基因编码工具进行追踪、 监测和操纵多种物种的神经回路。在此，我们建议开发一个 创新模型揭示了视觉引发的攻击行为背后的电路。我们将开发先进的 研究视觉触发所涉及的神经元回路和计算的工具和实验装置 暹罗斗鱼（Betta splendens）的攻击性。斗鱼经过选择性培育，具有高度攻击性 数百代人。他们现在拥有快速、稳健、刻板的攻击性表现，以应对 看到另一条鱼，因此为拟议的研究提供了一个理想的模型。 我们将首先测试视觉诱发的攻击行为是否会影响接收信号的电路中的特定节点 视觉输入（目标 1）。我们将识别这些节点，以便针对它们进行神经元活动分析。这 将通过三步过程来实现。首先，我们将使用以下方法在解剖学上追踪视觉攻击回路 来自视网膜的顺行示踪剂和来自肌肉的逆行示踪剂专门用于 表现出攻击性。然后，我们将识别引发攻击性的视觉线索的显着特征，以开发 强烈引起攻击性的视觉刺激和仅引起视觉注意但不引起攻击的其他刺激 侵略。最后，我们将识别攻击期间活跃的神经元（使用针对 pS6 的抗体，pS6 是一种标记物） 神经元活动），但当鱼看到引起注意但不具有攻击性的对照电影时则不然。一起， 这将使我们能够识别涉及视觉诱发攻击的节点，因此我们可以针对它们进行攻击 神经元活动分析。 然后，我们将开发转基因 Betta，在大脑中表达基因编码的钙指示剂，以 测量触发攻击性的视觉刺激是如何表达和处理的（目标 2）。最后，我们将 开发一种头部固定制剂来记录行为鱼类的神经元活动，首先关注鱼类同系物 哺乳动物杏仁核（目标 3）。这种大规模和细胞级分辨率的方法将使我们能够 研究涉及不同攻击性视觉刺激的感知和辨别的计算 诱导水平并生成将神经元活动与行为输出联系起来的模型。 本应用中开发的模型将提供一个独特而强大的平台来阐明 视觉诱发攻击行为背后的神经回路，我们希望作为后续项目呈现 针对BCP R01。