Mechanisms of Naturally-occurring Odor Valence Modulation

摘要 感官知觉不仅取决于刺激的物理属性，而且还受到内部因素的调节 状态包括注意力、荷尔蒙状态和新陈代谢以及经验和环境刺激。 神经系统如何整合这些综合信息来选择合适的行为 特定感官输入的输出？要解决这个问题，关键是要将特定的神经元活动与 行为或感觉。嗅觉系统提供了一个独特的机会来研究基因如何定义 电路产生特定的行为。此外，气味的感知效价和相应的 行为反应可能依赖于状态和环境，这使其成为研究感觉调节的理想模型。 在这里，我建议使用一个强大的新模型，涉及到气味价态的自然开关，以揭示 神经编码策略是感觉调节的基础。在这个模型中，雌性小鼠的价反应 对于男性来说，不稳定的社交暗示在很大程度上取决于发情状态。此外，观察到的行为变化 需要一个明确的嗅觉感受器，它在主要的嗅觉上皮细胞中表达。这是自然发生的 气味价态的转换提供了一个难得的机会来研究一种非条件性的，潜在的可诱导的变化 感知力。具体目标1将确定激素在观察到的气味价态调节中的作用。特定的 目标2将使用一种新开发的头部固定气味效价测试，该测试结合了清醒时的生理记录 小鼠同时进行行为分析以剖析状态依赖的外周和中枢机制 价态调制。这项工作将是识别潜在调制的神经电路的关键第一步。 并将阐明特定的感知特征是如何在神经系统中编码的。

Summary Sensory perception depends not only on the physical properties of the stimulus, but is also modulated by internal states including attention, hormonal status and metabolism as well as experience and environmental stimuli. How does the nervous system integrate this comprehensive information to select an appropriate behavioral output for a particular sensory input? To address this question, it is crucial to link specific neuronal activity to behaviors or percepts. The olfactory system provides a unique opportunity to study how genetically defined circuits give rise to specific behaviors. Moreover, the perceived valence of odors and the corresponding behavioral reactions can be state- and context-dependent, making it an ideal model to study sensory modulation. Here, I propose to use a powerful new model involving a naturally occurring switch in odor valence, to reveal the neuronal coding strategies underlying sensory modulation. In this model, the valence response of female mice to a male volatile social cue significantly depends on the estrus-state. Moreover, the observed change in behavior requires a defined olfactory receptor, which is expressed in the main olfactory epithelium. This naturally occurring switch in odor valence provides a rare opportunity to study a non-conditioned, potentially inducible change in perception. Specific Aim 1 will determine the role of hormones in the observed odor valence modulation. Specific Aim 2 will use a newly developed head-fixed odor valence assay that combines physiological recordings in awake mice with simultaneous behavioral analysis to dissect the peripheral and central mechanisms of state dependent valence modulation. This work will be a key first step to identify the neural circuitry underlying modulation of olfactory perception and will shed light on how specific perceptual features are encoded in the nervous system.