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.

项目摘要 攻击性是一种基本的社会行为。虽然普遍存在，但调节攻击性的刺激 不同物种之间的差异。灵长类动物强烈依赖视觉线索，而啮齿动物和昆虫的嗅觉刺激 必不可少的。由于老鼠和苍蝇是现代攻击性研究的主要模型，通过 哪些视觉神经回路调节了攻击性，目前还很大程度上尚不清楚。基因组研究的最新进展 测序、转基因和病毒技术允许应用基因编码工具进行追踪， 监测和操控各种物种的神经回路。在这里，我们建议开发一种 创新的模型，揭示了视觉攻击背后的电路。我们将发展先进的 研究视觉触发所涉及的神经元电路和计算的工具和实验装置 暹罗斗鱼(斗鱼)的攻击性。斗鱼被选择性地培育成高度攻击性 数百代人以来。他们现在有一种快速、强大和刻板印象的攻击性表现，以回应 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性是否会在接收到 视觉输入(目标1)。我们将识别这些节点，以便将它们作为分析神经元活动的目标。这 将通过三个步骤来实现。首先，我们将对视觉攻击回路进行解剖学追踪 视网膜的顺行示踪剂和肌肉的逆行示踪剂仅在 攻击性表现出来。然后，我们将确定攻击的显著特征-触发视觉线索，以开发 强烈地引起攻击性的视觉刺激和其他仅引起视觉注意但没有 攻击性。最后，我们将识别在攻击过程中活跃的神经元(使用针对标记pS6的抗体 神经元活动)，但当鱼看到一部引起注意而不是攻击性的控制性电影时就不会了。一起， 这将使我们能够识别与视觉诱发的攻击有关的节点，以便我们可以针对它们 对神经元活动的分析。 然后，我们将开发转基因斗鱼，在大脑中表达遗传编码的钙指示器，以 测量触发攻击性的视觉刺激是如何表现和处理的(目标2)。最后，我们将 开发一种头部固定装置来记录鱼类行为中的神经元活动，首先集中在鱼类同源物上 哺乳动物的杏仁核(目标3)。这种大规模和细胞级别的分辨率方法将使我们能够 研究不同攻击性的视觉刺激的感知和辨别所涉及的计算-- 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。 在此应用程序中开发的模型将提供一个独特而强大的平台来阐明 视觉诱发攻击的神经回路，我们希望将这个项目作为后续的 目标BCP R01。