Abstract

Fluid turbulence is a double-edged sword for the navigation of macroscopic animals, such as birds, insects, and rodents. On one hand, turbulence enables pheromone communication among mates and the possibility of locating food by their odors from long distances. Molecular diffusion would indeed be unable to spread odors over relevant distances in natural conditions. On the other hand, turbulent flows are hard to predict, and learning effective maneuvers to navigate them is challenging, as we discuss in this review. We first provide a summary of the olfactory organs that sense airborne or surface-bound odors, as well as the computational tasks that animals face when extracting information useful for navigation from an olfactory signal. A compendium of the dynamics of turbulent transport emphasizes those aspects that directly impact animals’ behavior. The state of the art on navigational strategies is discussed, followed by a concluding section dedicated to future challenges in the field.

流体湍流对于大型动物（如鸟类、昆虫和啮齿动物）的导航来说是一把双刃剑。一方面，湍流使得配偶之间的费洛蒙交流成为可能，并且能够通过气味从远距离定位食物。实际上，在自然条件下，分子扩散无法将气味传播到相关距离。另一方面，湍流难以预测，学习有效的机动以导航它们是具有挑战性的，正如我们在本综述中讨论的那样。我们首先总结了感知空气中或表面附着气味的嗅觉器官，以及动物在从嗅觉信号中提取有用导航信息时所面临的计算任务。对湍流传输动态的汇编强调了直接影响动物行为的那些方面。接下来讨论了导航策略的最新进展，最后一节专门讨论了该领域未来的挑战。

Introduction

Animals sense chemicals in their environment and use them to identify objects and locations. These chemicals or odors, sensed with specialized olfactory organs, are also used by animals to navigate toward or away from objects or locations. The strategies animals employ to navigate are likely to be different depending on the spatiotemporal distribution of chemical cues available for sampling. In this review, we discuss how odor landscapes are defined by physical properties of the world and how they constrain olfactory searches, as sketched in Figure 1. We restrict ourselves to terrestrial animals and emphasize navigation in naturalistic conditions, which typically involve turbulent and strongly fluctuating odor cues.

动物感知环境中的化学物质，并利用它们来识别物体和位置。这些化学物质或气味通过专门的嗅觉器官被感知，动物也利用它们来导航，朝向或远离特定的物体或位置。动物采用的导航策略可能会因可供采样的化学线索的时空分布而有所不同。在本综述中，我们讨论了气味景观如何由世界的物理属性定义，以及它们如何限制嗅觉搜索，如图1所示。我们将讨论范围限制在陆地动物，并强调在自然条件下的导航，这通常涉及湍流和强烈波动的气味线索。

Odor landscapes and search strategies. The following schematic illustrates how the physics of chemical transport dictates the frequency and smoothness of stimulus encounters by navigating animals. (a) At microscopic scales, molecular diffusion generates smooth changes in concentrations of chemicals, allowing for gradient ascent. (b) In flow regimes close (tens of centimeters) to typical naturalistic sources, even if large fluctuations are present, odor concentration changes are still smooth, and an animal receives some signal most of the time. Gradient ascent strategies, or variants that approximate them, are still sufficient. (c) At distances on the order of meters or larger, odors are significantly dispersed such that an animal encounters stimuli infrequently and intermittently. Because local gradients are largely random in relation to the source direction at the relevant time scales, simple gradient ascent is not feasible for navigation. (d) Trail tracking is unique in that the stimulus is relatively stationary but spatially sparse. How animals combine ground and airborne cues by alternately sampling sniffs from the ground and in the air remains by and large unexplored.

气味景观和搜索策略。下图说明了化学传输的物理学如何决定导航动物遇到刺激的频率和平滑度。

(a) 在微观尺度上，分子扩散产生化学浓度的平滑变化，允许梯度上升。

(b) 在接近典型自然源（几十厘米）的流动状态下，即使存在大幅波动，气味浓度变化仍然平滑，动物大部分时间都能接收到一些信号。梯度上升策略或其变体仍然足够。

(c) 在米级或更大的距离上，气味被显著分散，动物不经常且间歇性地遇到刺激。由于在相关时间尺度上局部梯度与源方向基本上是随机的，因此简单的梯度上升对于导航来说是不可行的。

(d) 跟踪路径是独特的，因为刺激相对静止但空间稀疏。动物如何通过交替从地面和空气中采样嗅闻来结合地面和空气线索在很大程度上仍未被探索。

HOW ARE ODORS SENSED? OLFACTORY NEUROBIOLOGY

Physical Features of Sensory Organs

Odors sensed by navigating animals are structured by environmental constraints. Chemical sensors and the organs that house them have a certain spatial extent and dynamics that define the spatiotemporal sampling of odors. Sensors vary in geometry—Drosophila antennae are on a scale of a millimeter and antennae of moths can measure tens of millimeters long, with a large surface area created by branching. In terrestrial mammals, olfactory sensory organs vary widely, and in the commonly studied olfactory animals, mice and rats, the nostrils are on a spatial scale of a centimeter. Olfactory sensing organs in higher animals come in pairs, each of which could sample independent volumes at distinct times and aid in odor navigation as we discuss below.

动物导航时感知的气味受到环境约束的结构化。化学传感器及其所处的器官具有一定的空间范围和动态特性，定义了气味的时空采样。传感器在几何形状上有所不同——果蝇的触角尺度为毫米，而蛾类的触角可以达到数十毫米长，并通过分支形成较大的表面积。在陆地哺乳动物中，嗅觉感知器官差异很大，在常见的嗅觉动物小鼠和大鼠中，鼻孔的空间尺度为厘米。高等动物的嗅觉感知器官成对存在，每个器官可以在不同时间采样独立的体积，并有助于气味导航，正如我们下面讨论的那样。

Animals sample odors by active inhalation of air into the nasal cavity, which houses the olfactory sensors. Odor sampling in mammals is coupled to respiration, which can be modulated voluntarily in terms of both frequency of sampling and volume sampled. The complex geometry of the nasal cavity and the external nostrils make it difficult to infer the details of odor transport in and around this sense organ prior to sensory transduction. Empirical and computational studies have suggested that certain physicochemical features of the odor environment might be extracted, in principle, thanks to the geometry of, and the fluid dynamics in, the nasal cavity. Evidence for such matching between the distribution of cellular sensors and the heterogeneous patterns of odors in the nasal cavity remains scarce.

动物通过主动吸入空气进入鼻腔来采样气味，鼻腔内有嗅觉传感器。哺乳动物的气味采样与呼吸相结合，呼吸频率和采样体积都可以自愿调节。鼻腔和外鼻孔的复杂几何结构使得在感觉传导之前推断气味在该感官内外的传输细节变得困难。实证和计算研究表明，凭借鼻腔的几何形状和流体动力学，原则上可以提取气味环境的某些物理化学特征。然而，目前关于细胞传感器分布与鼻腔中气味异质模式之间匹配的证据仍然很少。

Active sampling by mammals through sniffing may have parallels in insects, which can move their antennae to sample odors. Antennal movements can be induced by odors or by airflow, and might aid more efficient sensing, but how these movements are used for odorguided navigation is not yet clear.

哺乳动物通过嗅闻进行主动采样，这在昆虫中可能有类似之处，昆虫可以移动触角来采样气味。触角运动可以由气味或气流引起，可能有助于更有效的感知，但这些运动如何用于气味引导的导航尚不清楚。

Sensory Neurons

Odorants are detected by olfactory sensory neurons (OSNs), also referred to as olfactory receptor neurons (see Figure 2 for a schematic of the early olfactory system). In mammals, the cilia of the OSNs are embedded in the mucus layer, which is exposed to the flow in the nasal cavity. Molecules of odorants are transported/advected from the air to the mucus, where they are sorbed to the surface (by adsorption or absorption) and diffuse into the bulk. Insect sensory neurons are housed within structures called sensilla, which are filled with endolymph that protects the dendrites of OSNs. Olfactory binding proteins are present in high concentration in the mucus and endolymph and are thought to aid delivery of hydrophobic odorants to the aqueous environment in which the sensory neurons are embedded.

气味分子由嗅觉感受神经元（OSNs）检测，也称为嗅觉受体神经元（见图2，早期嗅觉系统的示意图）。在哺乳动物中，OSNs的纤毛嵌入在粘液层中，该层暴露在鼻腔的气流中。气味分子从空气中被运输/对流到粘液中，在那里它们通过吸附或吸收附着在表面并扩散到主体中。昆虫的感官神经元位于称为感受器的小结构内，这些结构充满了内淋巴，保护OSNs的树突。嗅觉结合蛋白在粘液和内淋巴中浓度很高，被认为有助于将疏水性气味分子输送到感官神经元所嵌入的水环境中。

Scheme of neural architectures that sense and process olfactory stimuli. (a) Schematic of the nasal cavity and the neural components involved in olfaction in mice (sagittal plane). Airflow brings odors over the olfactory epithelium during inhalation. OSNs are electrically activated by odors and signal to the brain through their axons converging on glomeruli in the OB (light blue). Processed information is carried from the OB to multiple brain areas by MTCs. (b) Schematic of the Drosophila olfactory system. OSNs are housed inside structures called sensilla in the antennae (OSN shown outside sensilla for clarity) and project to the AL. PNs receive sensory input and project to multiple brain structures including the mushroom body. (c) Common neural circuit motif in rodents and insects. OSNs expressing a particular receptor type out of a large repertoire (indicated by like colors) converge selectively in individual glomeruli in the OB, making connections with MTCs or PNs. Local circuit elements in the OB or AL include inhibitory neurons (shown as a black circle) that receive excitation from MTCs/PNs and reciprocally inhibit them. MTCs/PNs project to multiple brain regions, including the piriform cortex/mushroom body, where they are thought to make dispersed, random, and sparse connections (shown as intersecting wires, with connections denoted by small circles). Abbreviations: AL, antennal lobe; MTCs, mitral/tufted cells; OB, olfactory bulb; OSNs, olfactory sensory neurons; PN, principal neuron.

嗅觉刺激感知和处理的神经结构示意图。

(a) 鼻腔和小鼠嗅觉相关神经成分的示意图（矢状面）。吸气时，气流将气味带到嗅觉上皮。气味电激活 OSNs，并通过其轴突向大脑发出信号，这些轴突在嗅球（OB）（浅蓝色）中的球状体汇聚。处理后的信息由 MTCs 从 OB 传送到多个大脑区域。

(b) 果蝇嗅觉系统的示意图。OSNs 位于触角中的称为感受器的结构内（为清晰起见，OSN 显示在感受器外部），并投射到 AL。PNs 接收感觉输入并投射到包括蘑菇体在内的多个大脑结构。

(c) 啮齿动物和昆虫中的常见神经回路模式。在大量受体类型中表达特定受体类型的 OSNs（由相似颜色表示）选择性地在 OB 中的单个球状体中汇聚，与 MTCs 或 PNs 建立连接。OB 或 AL 中的局部电路元件包括抑制性神经元（显示为黑色圆圈），它们从 MTCs/PNs 接收兴奋并相互抑制它们。MTCs/PNs 投射到多个大脑区域，包括 piriform 皮层/蘑菇体，它们被认为建立分散、随机和稀疏的连接（显示为相交的导线，连接由小圆圈表示）。

Odorants solubilized in the mucus (or endolymph) reach the OSNs and bind to odorant receptors (ORs). This binding triggers a transduction pathway that controls the opening of plasma membrane ion channels and subsequent voltage changes in the OSN. In all species of animals investigated, ORs comprise a family with dozens to over a thousand members. The biology of ORs varies widely and includes both ligand-gated ion channels and G-protein coupled receptors (GPCRs). Several recent reviews offer summaries of many receptor families and their transduction mechanisms. A key feature of all ORs that is relevant for the topic of this review is their kinetics, especially under conditions of intermittent and fluctuating odor encounters likely to occur in natural conditions. The major type of ORs in mammals belongs to the GPCR family. Like other members of this family, mammalian ORs exhibit many complex properties such as agonism and antagonism for different ligands, as well as adaptation. ORs in insects are heteromeric ion channels that exhibit rapid kinetics and adaptation. Adaptation to stimulus features has been tied to computational advantages such as preserving coding fidelity in insect ORs, but the functional roles of receptor adaptation in mammalian OSNs is not understood in quantitative and normative detail.

溶解在粘液（或内淋巴）中的气味分子到达 OSNs 并与气味受体（ORs）结合。这种结合触发了一个传导途径，控制质膜离子通道的开放以及随后 OSN 的电压变化。在所有研究过的动物物种中，ORs由几十到一千多个成员组成。ORs的生物学差异很大，包括配体门控离子通道和 G 蛋白偶联受体（GPCRs）。几篇近期综述总结了许多受体家族及其传导机制。本综述主题相关的所有 ORs 的一个关键特征是它们的动力学，特别是在自然条件下可能发生的间歇性和波动性气味遇到条件下。哺乳动物中主要类型的 ORs 属于 GPCR 家族。与该家族的其他成员一样，哺乳动物 ORs 表现出许多复杂特性，如对不同配体的激动和拮抗作用，以及适应性。昆虫中的 ORs 是异源离子通道，表现出快速动力学和适应性。对刺激特征的适应性已与计算优势联系在一起，例如在昆虫 ORs 中保持编码保真度，但哺乳动物 OSNs 中受体适应性的功能作用尚未以定量和规范的细节理解。

In broad terms, receptors tend to be activated by a diverse array of ligands (agonists) with different binding affinities and potentially blocked by antagonists. A fundamental principle is that odorant identity is coded by a combinatorial activation of multiple receptors, with the timing or latency of activation potentially playing a privileged role. Some pheromones are thought to act through dedicated receptors, but even there exclusive and selective recognition of pheromones by individual receptors is not always proven. Although a large fraction of studies have used single odorants to activate receptors, natural smells are mixtures of many chemical species. Several recent studies have provided strong evidence for highly nonlinear effects of odorant mixtures, with antagonistic interactions dominating. Behavioral implications of these nonlinear interactions have yet to be fully understood, especially in the context of odorguided navigation in natural environments.