Interrogating the Neural Representations of Innately Aversive Predator Odors

询问天生厌恶的捕食者气味的神经表征

• 批准号: 8782991
• 负责人: Taralyn Marie Tan
• 金额: $ 3.01万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782991
• 关键词: Afferent Neurons; Animals; Anxiety; Anxiety Disorders; Axon; Behavior; Behavioral; Behavioral Assay; Brain; Cells; Cues; Disease; Dorsal; Environment; Epithelial; Exhibits; Food; Fright; Functional Imaging; Hazardous Chemicals; Image; Immunohistochemistry; Individual; Label; Laboratories; Lateral; Lead; Ligands; Maps; Mediating; Microscopy; Mus; Odorant Receptors; Odors; Operative Surgical Procedures; Optics; Output; Panic Disorder; Partner in relationship; Pattern; Population; Post-Traumatic Stress Disorders; Preparation; Process; Property; Recruitment Activity; Relative (related person); Reproduction; Sensory; Smell Perception; Source; Specialist; Stereotyped Behavior; Stereotyping; Stimulus; Structure; System; Techniques; Testing; Translating; calcium indicator; combinatorial; effective therapy; experience; in vivo; insight; molecular marker; nervous system disorder; neural circuit; novel; olfactory bulb; olfactory receptor; public health relevance; receptor; relating to nervous system; research study; response; sensory stimulus

DESCRIPTION (provided by applicant): The ability to detect and correctly respond to environmental stimuli is critical for survival. Our sense of olfaction enables us to locate food sources, reject food that is spoiled and avoid potential dangers such as hazardous chemicals. It is poorly understood how the brain organizes olfactory information into meaningful representations of the outside world to direct adaptive behavioral responses. To understand how specific olfactory cues can lead to behavior, we will probe the organization of the neural circuits mediating innate, odor- induced aversion in the mouse. Mice exhibit innate avoidance and fear behaviors in response to odors emitted by potentially dangerous predators; these innate behavioral responses are stereotyped in form, suggesting that the neural representations for behaviorally relevant odorants are genetically hard-wired in the mouse. In Aim 1 we propose to employ a surgical and imaging preparation we have developed in the laboratory to map predator odor-driven neural responses in the olfactory bulb (OB), the first relay of olfactory information in the brain. These experiments will test the hypothesis that all predator odorants activate a small, spatially restricted region of the OB, which would suggest that information for behaviorally important classes of odorants is spatially organized into subdomains of the OB that may mediate innate odor-evoked behavioral responses. In Aim 2 we propose to interrogate the tuning properties of the primary olfactory sensory neurons (OSNs) - and thus the receptors expressed by those cells - that detect various predator odors by presenting a large odorant set to the mouse and assessing whether the glomeruli that respond to predator odors also respond to any other odorants in the test set. These experiments will provide insight into whether predator odors are encoded via a select number of "specialist receptors" that are narrowly tuned to detect their specific ligand, or whether predator cues are encoded in a combinatorial manner via broadly tuned olfactory receptors. Together, these experiments will provide insight into how information about an entire class of ethologically relevant odorants is organized in the brain. By revealing general principles by which the mammalian brain detects and processes behaviorally meaningful odorants, the proposed experiments will provide a conceptual framework to ultimately understand how the neural circuits mediating odor-evoked behaviors are modified by experience and disease.

描述(由申请人提供)：检测和正确响应环境刺激的能力对生存至关重要。我们的嗅觉使我们能够定位食物来源，拒绝变质的食物，并避免危险化学品等潜在危险。人们对大脑如何将嗅觉信息组织成对外部世界有意义的表征以指导适应性行为反应的方式知之甚少。为了了解特定的嗅觉线索如何导致行为，我们将探索调节小鼠天生的气味诱导厌恶的神经回路的组织。老鼠对潜在危险的捕食者发出的气味表现出天生的回避和恐惧行为；这些天生的行为反应在形式上是刻板的，这表明与行为相关的气味的神经表征在老鼠身上是天生的。在目标1中，我们建议使用我们在实验室开发的外科和成像准备来定位嗅球(OB)中捕食者气味驱动的神经反应，嗅球是大脑中嗅觉信息的第一个中继器。这些实验将检验这样一个假设，即所有捕食者气味都激活了OB的一个小的、空间上受限的区域，这将表明行为上重要的气味类别的信息在空间上被组织到OB的子域中，这些子域可能介导先天气味诱发的行为反应。在目标2中，我们建议询问初级嗅觉神经元(OSNs)的调谐特性--因此这些细胞表达的受体--通过向小鼠呈现一个大的气味集并评估对捕食者气味做出反应的肾小球是否也对测试集中的任何其他气味做出反应来检测各种捕食者气味。这些实验将提供洞察，了解捕食者气味是通过选定数量的“专家受体”编码的，这些“专家受体”被狭隘地调谐来检测其特定的配体，或者捕食者线索是否通过宽调谐的嗅觉接收器以组合的方式编码。总之，这些实验将提供关于整个类别的行为学相关气味的信息是如何在大脑中组织的洞察力。通过揭示哺乳动物大脑检测和处理有行为意义的气味的一般原理，拟议的实验将提供一个概念框架，最终理解介导气味诱发行为的神经回路是如何被经验和疾病改变的。