Acoustic modulation of forebrain aggression network in miniature, transparent vocal fish

微型透明发声鱼前脑攻击网络的声学调制

• 批准号: 10524567
• 负责人: ANDREW H BASS
• 金额: $ 73.8万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524567
• 关键词: Acoustics; Adult; Aggressive behavior; Anatomy; Antibodies; Area; Auditory; Behavioral; Biological Models; Birds; Brain; Brain imaging; Brain region; Calcium; Cell Nucleus; Distal; Esthesia; Female; Fishes; Future; Genetic; Genetic Models; Goals; Green Fluorescent Proteins; Hearing; Human; Hypothalamic structure; Image; Individual; Injury; Label; Mammals; Maps; Mediating; Methods; Modeling; Muscle; Nervous system structure; Neurons; Neurosciences; Neurotransmitters; Opsin; Optics; Outcome; Output; Pathway interactions; Pharmacology; Photons; Phylogenetic Analysis; Physiological; Play; Population; Posture; Primates; Property; Prosencephalon; Role; Signal Transduction; Social Behavior; Social Environment; Sonication; Specificity; Stimulus; Telencephalon; Testing; Transgenic Organisms; Vertebrates; Visual; Visualization; Zebrafish; auditory stimulus; excitatory neuron; fighting; innovation; male; neural circuit; neural model; optogenetics; prevent; promoter; relating to nervous system; sensory integration; social; sound; tool; visual stimulus; vocalization

Assessing social signals, such as vocalizations, figures prominently in the outcome of aggressive encounters, including the potential to win a fight or prevent escalation resulting in physical injury. Among vertebrates, the neural circuitry integrating sensation, for example what an individual hears, with modulation of aggressive output, is distributed throughout the forebrain and conserved across vertebrate lineages. Social behavior is thought to be an emergent property of activity across this network, and audition plays a prominent role in modulating aggression in primates and birds. In mammals, although sensory integration within specific forebrain regions is thought to strongly influence aggressive behavior, approaches to examining and understanding this integration remain a challenge, in part because of the large size of mammalian brains and limits on brain-wide optical access to the full network. To overcome this problem, we propose a new model, Danionella dracula, a genetically tractable miniature species of fish that is transparent into adulthood, produces robust sonic and visual (postural) signals solely in aggressive contexts, and a close relative of zebrafish (Danio rerio), which are not sonic. Genetic toolkits developed in zebrafish are readily adapted in D. dracula. Our long- term goal is to use this new model to test if an evolutionarily conserved forebrain network of neuronal populations is activated during aggression, sensitive to acoustic signals, and, using optogenetic approaches, can be manipulated at the cellular level to effect aggressive behavior. To reach this goal, we propose in Aim 1 to map a forebrain aggression network in D. dracula and use cutting-edge methods for brain-wide 2 and 3- photon calcium imaging of auditory-responsive neurons to identify forebrain regions involved specifically in acoustic-related aggression. Aim 2’s goal is to map projections and gain genetic access to a brain region identified in Aim 1 for identifying connectivity and causal testing of a role for this region in aggression and on activity across the aggression network. To this end, we will generate a transgenic line with GCaMP and photoactivatable green fluorescent protein (paGFP), that will allow visualization of projections in functionally characterized neurons, uncovering anatomical pathways between auditory neurons within aggression circuits. Using a promoter characterized in zebrafish Gal4 lines we will create a transgenic D. dracula line expressing an opsin in a population of excitatory neurons in an auditory-sensitive region and determine their connectivity to other candidate brain areas involved in aggression. Completion of these aims will provide the necessary transgenic lines and methods to establish D. dracula as a new vertebrate model for neural circuits of aggression. The small size, transparency, and robust sonic-aggressive behaviors of this species’ adults, and phylogenetic relationship to zebrafish will allow genetic and brain-wide optical interrogation of sensory integration within neural circuits underlying vertebrate social behavior. The results will be the basis for a BCP R01 investigating how acoustic and other (e.g., visual-postural) stimuli modulate aggression.

评估社会信号（例如发声），在侵略性相遇的结果中显着地数字， 包括赢得战斗或防止升级导致身体伤害的潜力。在脊椎动物中， 神经回路整合感觉，例如个人听到的声音，并调节侵略性 输出分布在整个前脑，并在脊椎动物谱系上配置。社会行为是 被认为是该网络中活动的紧急特性，试镜在 调节初级和鸟类的侵略性。在哺乳动物中，尽管特定的感觉积分 人们认为前脑区域会强烈影响攻击性行为，检查和 了解这种整合仍然是一个挑战，部分原因是哺乳动物的大脑和 限制了全网络范围的光学访问。为了克服这个问题，我们提出了一个新模型， Danionella dracula是一种透明到成年的鱼类的典型微型鱼类，可产生 强大的声音和视觉（姿势）信号仅在侵略性的环境中，而斑马鱼的亲戚（Danio） rerio），不是声音。斑马鱼中开发的遗传工具包在D. Dracula中很容易适应。我们的长期 术语目标是使用该新模型测试神经元的进化保守的前脑网络是否 在侵略性期间激活种群，对声学信号敏感，并使用光遗传学方法， 可以在细胞水平上操纵以实现攻击行为。为了实现这一目标，我们在目标1中提出建议 绘制D. Dracula中的前脑侵略性网络，并使用尖端的方法对大脑2和3-- 听觉响应神经元的光子钙成像，以鉴定特有的前脑区域 与声学有关的侵略性。 AIM 2的目标是绘制预测并获得遗传进入大脑区域 在AIM 1中识别以识别该地区在侵略性和ON的连通性和因果测试 跨积极网络的活动。为此，我们将使用GCAMP生成一条转基因线 光活化绿色荧光蛋白（PAGFP），它将允许在功能上可视化项目 表征神经元，揭示了侵略性电路中听觉神经元之间的解剖途径。 使用以斑马鱼GAL4线为特征的启动子，我们将创建一个转基因D. D. D. D. Dracula线表达 在听觉敏感区域中的兴奋性神经元种群中的蛋白蛋白并确定其连通性 到其他参与侵略性的候选大脑区域。这些目标的完成将提供必要的 转基因线和方法是建立d。dracula作为神经回路的新脊椎动物模型 侵略。该物种成年人的小尺寸，透明和强大的声音攻击行为，以及 系统发育与斑马鱼的关系将允许对感觉的遗传和脑部的光学询问 脊椎动物社会行为的神经回路内的整合。结果将是BCP的基础 R01调查了声学和其他（例如视觉 - 波经）刺激如何调节攻击性。