Interrogating the Neural Representations of Innately Aversive Predator Odors

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找到食物来源，拒绝变质的食物，避免潜在的危险，如危险化学品。人们对大脑如何将嗅觉信息组织成外部世界的有意义的表征以指导适应性行为反应知之甚少。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先天性气味诱导厌恶的神经回路的组织。小鼠表现出先天的回避和恐惧行为，以应对潜在危险的捕食者发出的气味;这些先天的行为反应是定型的形式，这表明行为相关的气味的神经表征是遗传硬连线的小鼠。在目标1中，我们建议采用我们在实验室中开发的手术和成像准备，以映射嗅球（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。这些实验将测试的假设，所有的捕食者气味激活一个小的，空间限制区域的OB，这将表明，信息的行为重要类别的气味在空间上组织成子域的OB，可能介导先天的气味诱发的行为反应。在目标2中，我们提出询问初级嗅觉感觉神经元（OSN）的调谐特性-以及这些细胞表达的受体-通过向小鼠提供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捕食者的气味是否编码通过选择数量的“专业受体”，这些受体被狭隘地调整，以检测其特定的配体，或者是否捕食者的线索编码在一个组合的方式通过广泛调整的嗅觉受体。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行为上有意义的气味的一般原理，拟议的实验将提供一个概念框架，以最终了解介导气味诱发行为的神经回路如何被经验和疾病所改变。

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.