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，如发声，在攻击性遭遇的结果中占突出地位， 包括赢得战斗或防止导致身体伤害的升级的可能性。在脊椎动物中， 整合感觉的神经回路，例如个体听到的声音， 输出，分布在整个前脑和保存在脊椎动物谱系。社会行为是 被认为是在这个网络中活动的一个紧急属性，而听觉在其中扮演着重要的角色。 调节灵长类和鸟类的攻击性。在哺乳动物中，虽然感觉整合在特定的 前脑区域被认为强烈影响攻击行为，检查方法和 理解这种整合仍然是一个挑战，部分原因是哺乳动物大脑的体积很大， 限制了全脑范围的光学访问整个网络。为了克服这个问题，我们提出了一个新的模型， Danionella dracula是一种遗传上易于控制的微型鱼类，成年后是透明的， 仅在攻击性环境中发出强烈的声音和视觉（姿势）信号，是斑马鱼的近亲（Danio rerio），这不是声波。在斑马鱼中开发的遗传工具包很容易适应D。德古拉我们长久以来- 长期目标是使用这个新模型来测试进化保守的前脑神经元网络是否 种群在攻击过程中被激活，对声学信号敏感，并且，使用光遗传学方法， 可以在细胞水平上被操纵以影响攻击性行为。为了实现这一目标，我们在目标1中提出 来绘制D.德古拉和使用尖端的方法，为脑宽2和3- 光子钙成像的神经反应神经元，以确定前脑区域，特别是参与 与声音有关的攻击AIM 2的目标是绘制投影图并获得大脑区域的遗传通路 在目标1中确定的，用于确定该地区在侵略中的作用的连通性和因果关系测试， 攻击性网络中的活动为此，我们将产生具有GCaMP的转基因系， 光活化绿色荧光蛋白（paGFP），这将允许可视化的投影功能， 特征神经元，揭示了侵略电路内听觉神经元之间的解剖通路。 使用斑马鱼Gal 4系中特征性的启动子，我们将创建转基因D.德古拉线表达 视蛋白在兴奋性神经元的群体中的神经敏感区域，并确定其连接 其他与攻击性有关的大脑区域实现这些目标将提供必要的 转基因系和建立D. dracula作为一种新的脊椎动物模型的神经回路 侵略该物种成年个体的小尺寸、透明性和强大的声波攻击行为， 与斑马鱼的系统发育关系将允许对感觉的遗传和全脑光学询问 整合在脊椎动物社会行为的神经回路中。结果将作为BCP的基础 R 01调查声学和其他（例如，视觉-姿势）刺激调节攻击性。