Behavioral and Neural Substrates of Odor-Guided Navigation in the Human Brain

人脑气味引导导航的行为和神经基础

• 批准号: 10366995
• 负责人: Jay A Gottfried
• 金额: $ 47.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366995
• 关键词: Address; Air; Alzheimer' s Disease; Animals; Basic Science; Behavior; Behavioral; Biological Assay; Birds; Brain; Categories; Cells; Characteristics; Code; Cognitive; Complement; Computing Methodologies; Cues; Data; Distal; Electroencephalography; Ensure; Environment; Floor; Functional Magnetic Resonance Imaging; Goals; Human; Imaging Techniques; Impairment; Insecta; Learning; Location; Mammals; Maps; Memory; Methods; Modeling; Movement; Nature; Neurobiology; Neurons; Neurosciences Research; Nose; Odors; Olfactory Pathways; Oral; Oral cavity; Organism; Pathway interactions; Patients; Pattern; Play; Poaceae; Positioning Attribute; Predictive Value; Predisposition; Prefrontal Cortex; Property; Psychophysics; Receptor Cell; Research; Rewards; Rodent; Role; Route; Sensory; Sleep; Smell Perception; Source; Space Perception; Stimulus; System; Techniques; Testing; Travel; Visual; Visuospatial; Work; base; behavior test; cell type; design; entorhinal cortex; experimental study; flexibility; high risk; human imaging; human subject; information processing; insight; interdisciplinary approach; neuromechanism; novel; piriform cortex; programs; relating to nervous system; response; sensory system; stability testing; two-dimensional; virtual; virtual reality; visual information; way finding

ABSTRACT Sensory systems have evolved to help meet the behavioral needs of organisms to ensure survival. Across the animal kingdom, two sensory functions are paramount: first, to identify specific objects in the environment and endow them with salience; and second, to move closer to objects of desire and away from objects that are best avoided. These properties – identification and localization – are the “what” and “where” questions of sensory information processing, respectively, and each of the senses provides a unique snapshot of the world that complements the other senses. In the unique case of olfaction, orthonasal and retronasal olfactory channels ensure that odor sources can be identified and tracked with fidelity at distal, proximate, and intraoral distances. This proposed project will focus on the “where” question of information processing in the human olfactory system. In particular, we aim to understand the capacities, constraints, and mechanisms by which odor cues orient and steer a navigator in the right direction. In this regard, a singular aspect of odors is their ability to travel through the air over long distances, such that the olfactory system can gather valuable predictive information not only about the physical location of an odorous source, but also about the navigator’s position within a physical landscape. Critically, while elegant neurobiological studies on odor navigation have been conducted in insects and birds, basic research on this topic in mammals, including humans, is sparse. Our planned studies are inspired by groundbreaking experiments showing that different types of neurons can encode and map physical spaces, including “place cells” (representing specific locations in space) and “grid cells” (representing an internal coordinate system to self-orient in this space). Here we will use functional magnetic resonance imaging (fMRI), virtual reality (VR) techniques, and computational methods to determine whether we can infer the presence of “grid-like” fMRI responses when human subjects navigate through an odor-rich two-dimensional landscape. In Aim 1, subjects will be asked to navigate a VR arena in which the only informative sensory cues are olfactory, enabling us to test whether subjects can learn the spatial relational positions among a set of odors, and whether grid-like responses arise during odor navigation. Aim 2 will test the stability of olfactory grid-like responses by assessing whether contextual changes in the VR arena induce remapping of olfactory cognitive maps. Aim 3 will test the behavioral limits of human olfactory navigation by progressively peeling away all remaining visual cues in the arena. Together these studies should bring fundamental understanding to the capacities and constraints of human olfactory navigation, and should highlight neural mechanisms underlying the “where” question of human olfaction, and more broadly, how the olfactory system tracks and locates odor sources in odiferous environments.

摘要 感觉系统已经进化，以帮助满足有机体的行为需求，以确保生存。在世界各地 在动物王国，有两种感觉功能是至关重要的：第一，识别环境中的特定物体和 赋予他们突出的地位；第二，走近渴望的对象，远离最好的对象 避免了。这些特性--识别和定位--是感官的“什么”和“在哪里”的问题 信息处理，每个感官都提供了一个独特的世界快照， 补充了其他感官。在嗅觉、正鼻和鼻后嗅觉通道的独特情况下 确保远端、近端和口腔内的气味来源能够被准确识别和跟踪。 这个拟议的项目将集中在人类嗅觉中信息处理的“哪里”问题上 系统。特别是，我们的目标是了解气味提示的能力、限制和机制 引导导航员朝着正确的方向前进。在这一点上，气味的一个独特方面是它们能够 通过长距离的空气传播，因此嗅觉系统可以收集有价值的预测 不仅是关于气味来源的物理位置的信息，还包括关于导航员位置的信息 在一片自然景观中。关键的是，虽然关于气味导航的优雅神经生物学研究 在昆虫和鸟类中进行的关于这一主题的基础研究在哺乳动物中，包括人类，是稀少的。 我们计划的研究是受到突破性实验的启发，实验表明不同类型的神经元可以 对物理空间进行编码和绘制地图，包括“位置单元”(代表空间中的特定位置)和“格网” 单元“(表示在该空间中自定向的内部坐标系)。在这里，我们将使用函数 磁共振成像(FMRI)、虚拟现实(VR)技术和计算方法 我们是否能推断出当人类受试者导航通过 气味浓郁的二维景观。在目标1中，受试者将被要求在一个VR竞技场中导航，在这个竞技场中，只有 信息性的感觉线索是嗅觉的，使我们能够测试受试者是否能够学习空间关系 一组气味中的位置，以及在气味导航过程中是否出现网格状反应。AIM 2将测试 通过评估VR领域的背景变化是否会导致嗅网格样反应的稳定性 重新绘制嗅觉认知地图。目标3将测试人类嗅觉导航的行为极限 逐渐剥离竞技场上所有剩余的视觉线索。这些研究加在一起应该带来 对人类嗅觉导航能力和限制的基本理解，并应 强调人类嗅觉“在哪里”问题背后的神经机制，更广泛地说，是如何 嗅觉系统跟踪和定位恶劣环境中的气味来源。