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

摘要 感官系统的进化是为了帮助满足生物体的行为需求，以确保生存。各地 在动物王国中，两种感觉功能是最重要的：第一，识别环境中的特定物体， 赋予它们显著性;第二，接近欲望的对象，远离最好的对象 避免了这些属性--识别和定位--是感官的“什么”和“在哪里”的问题。 信息处理，每一种感官都提供了一个独特的世界快照， 补充其他感官。在嗅觉的独特情况下，鼻前和鼻后嗅觉通道 确保可以在远端、近端和口内距离处准确识别和跟踪气味源。 这个项目将集中在人类嗅觉中信息处理的“何处”问题上 系统特别是，我们的目标是了解气味线索的能力，限制和机制， 为导航仪定向并将其引导到正确的方向。在这方面，气味的一个独特方面是它们能够 在空气中长距离传播，这样嗅觉系统就可以收集有价值的预测信息。 不仅关于气味源的物理位置，而且关于导航器的位置的信息 在一个物理景观中。重要的是，虽然关于气味导航的优雅神经生物学研究已经 在昆虫和鸟类中进行的这一专题的基础研究，在哺乳动物，包括人类中很少。 我们计划的研究受到开创性实验的启发，这些实验表明不同类型的神经元可以 编码和映射物理空间，包括“位置单元”（表示空间中的特定位置）和“网格 细胞”（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）技术和计算方法来确定 当人类受试者通过一个导航系统时，我们是否可以推断出“网格状”fMRI反应的存在， 气味丰富的二维景观。在目标1中，将要求受试者导航VR竞技场，其中唯一的 提供信息的感官线索是嗅觉的，使我们能够测试受试者是否能够学习空间关系 在一组气味中的位置，以及在气味导航期间是否出现网格状响应。目标2将测试 通过评估VR竞技场中的情境变化是否诱导嗅觉网格样反应的稳定性， 嗅觉认知地图的重新绘制。目标3将测试人类嗅觉导航的行为极限， 逐渐剥离竞技场中所有剩余的视觉线索。这些研究应该会带来 基本了解人类嗅觉导航的能力和限制，并应 强调了人类嗅觉“在哪里”问题的神经机制，更广泛地说， 嗅觉系统跟踪和定位气味环境中的气味源。

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.