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date: 20 January 2020

Navigation Towards the Source Through Chemosensory Strategies and Mechanisms

Summary and Keywords

Asymmetry of bilateral visual and auditory sensors has functional advantages for depth visual perception and localization of auditory signals, respectively. In order to detect the spatial distribution of an odor, bilateral olfactory organs may compare side differences of odor intensity and timing by using a simultaneous sampling mechanism; alternatively, they may use a sequential sampling mechanism to compare spatial and temporal input detected by one or several chemosensors. Extensive research on strategies and mechanisms necessary for odor source localization has been focused mainly on invertebrates. Several recent studies in mammals such as moles, rodents, and humans suggest that there is an evolutionary advantage in using stereo olfaction for successful navigation towards an odor source. Smelling in stereo or a three-dimensional olfactory space may significantly reduce the time to locate an odor source; this quality provides instantaneous information for both foraging and predator avoidance. However, since mammals are capable of finding odor sources and tracking odor trails with one sensor side blocked, they may use an intriguing temporal mechanism to compare odor concentration from sniff to sniff. A particular focus of this article is attributed to differences between insects and mammals regarding the use of unilateral versus bilateral chemosensors for odor source localization.

Keywords: odor navigation, sequential sampling, simultaneous sampling, vertebrates, invertebrates, odor plumes, stereo olfaction, sensors, rodents, bilateral asymmetry

Introduction

Odor source localization is essential for survival of most animal species, from microorganisms to mammals. They use sophisticated behavioral strategies and sensory computation to navigate toward desirable conditions in natural environments and away from threatening ones in their natural environments. Behaviorally, this is expressed in the search for food, in findings mates for proliferation, and when avoiding threats such as noxious food substances and predators. To accomplish these goals, terrestrial and marine invertebrates and vertebrates navigate in dynamic and complex environments by using olfaction. Odor molecules do not contain any spatial information. However, if odors are spread out in air, on water, or are deposited on surfaces, spatial and temporal information can be detected and used by the animals for navigation. Odor navigation is accomplished via single, bilateral, or multiple chemosensors, the geometrical organization of the sensors on the body, and the nature of sampling of chemical gradients—either active or passive. There are two phases in odor navigation: detection of the presence of an odor and steering towards its source. Source localization and tracking of chemosensory cues, such as odors and pheromones, involves walking (Borst & Heisenberg, 1982; Martin, 1965), flying (Frye, Tarsitano, & Dickinson, 2003; Nevitt, Losekoot, & Weimerskirch, 2008; van Breugel & Dickinson, 2014; Vickers, 2006), swimming (Gardiner & Atema, 2007; Hodgson & Mathewson, 1971), and crawling (Porter et al., 2007). In many cases, odor navigation requires integration of multisensory inputs and interplay between different behavioral strategies. Additionally, odor navigation may also involve learning, memory, and olfactory-based decision-making functions.

Two known fundamental strategies that determine the direction of a chemical source are distinguished: kinesis and taxis.

Navigation Towards the Source Through Chemosensory Strategies and Mechanisms

Figure 1. Basic strategies. Active sensation during orientation behavior in the Drosophila larva: more sense than luck. Main types of orientation behavior. (a) Operational criteria for classification of spatial orientation behavior into indirect (kinesis) and direct (taxis) responses; (b) illustration of the behavioral strategy demonstrated by bacteria (left), fruit fly larvae (center), and walking bees (right) in a chemical gradient. The trajectory of the body and chemosensors is represented as a plain and a dashed curve, respectively. Bacteria implement a biased random walk where runs are elongated in the direction of the gradient (klinokinesis). Fruit fly larvae are capable of directing their turns toward the gradient. This mechanism involves active sampling through lateral head movements (klinotaxis). To orient in an odor gradient, walking bees compare the inputs from their left and right antennae and veer toward the side of highest stimulation (tropotaxis).

(Gomez-Marin, Stephens, & Louis, 2012).

Kinesis

Kinesis is an indirect orientation of the organism towards or away from a stimulant, which is dependent on the intensity of stimulation. The organism samples the stimulus at a single point in space without reference to its own body orientation. There are two types of kinesis: orthokinesis and klinokinesis. In orthokinesis, the speed of locomotor movement alters with changes in the intensity of chemostimulation. In klinokinesis the rate of turning, or rate of change of direction, is proportional to the intensity of the stimulus. A process consisting of successive steps with random orientation can be modeled mathematically as a random walk. Random walk is an uncorrelated and unbiased locomotion, in which the orientation of each step is independent of prior steps (Berg, 1983; Codling, Plank, & Benhamou, 2008). One example is bacterial chemotaxis, which can be described by this biased random walk model. The microscopic organism bacterium Escherichia coli (E. coli) uses an elegant sensory infrastructure for successful outcomes (Berg, 2004; Berg & Brown, 1972; Berg & Purcell, 1977; Bren & Eisenbach, 2000). E. coli swims at speeds of 10–20 body lengths per second and propels itself by using a motoric unit—the flagellar complex. E. coli utilizes a combination of a chemosensory unit (cell surface receptor complex) and the flagellar complex, which work in concert via signal transduction pathways that transmit information between the two. The movements are either a run motion, resulting from a bias counterclockwise rotation of the flagellum, or a tumbling motion, resulting from a clockwise rotation of the flagellum. The advantage of tumbling movements is to allow the cells to randomly move sharply to new directions. During bias motion, the flagellar filaments form a trailing bundle that pushes the cell forward. For a tumbling movement, at least one of the flagellar motors reverses the filament direction to a clockwise direction that unevens the bundle. A messenger protein, CheY, transduces the signal from the sensors to the motoric unit. This binding changes the bias counterclockwise rotation to clockwise directional movement, resulting in tumbling motion. In isotropic chemical environments, E. coli presents a random walk by alternating periods of both run and tumbling movements in the preferred direction, toward attractants (such as amino acids and sugars) and away from noxious chemicals. Run motion is extended while tumbling is suppressed. E. coli detects gradients as a function of time by comparing present concentrations to the previous one; therefore, E.coli may use a short-term memory faculty for chemosensory behavior.

Klinokinesis was also broadly studied in Caenorhabditis elegans (C. elegans) (Dunn, Lankheet, & Rieke, 2007; Dunn, Lockery, Pierce-Shimomura, & Conery, 2004; Ferrée & Lockery, 1999; Ferrée, Marcotte, & Lockery, 1997) to show that large and sporadic turns lead to successful steering towards the stimulant (Pierce-Shimomura, Morse, & Lockery, 1999).

Taxis

Unlike kinesis, taxis is a direct orientation of the organism towards (positive) or away from (negative) the stimulant. The organism detects stimulus direction relative to its own body orientation, allowing deterministic navigation. In this case, the orientation is not random. Chemotaxis has been studied broadly on nematodes by examining their trails on a medium in the presence of a gradient of chemicals. C. elegans is also capable of using direct orientation towards the stimulant; this strategy is named klinotaxis. The use of klinotaxis allows C. elegans to slowly adjust its locomotor movements and to perform small turns that are oriented towards a favored source (Ferrée & Lockery, 1999; Iino & Yoshida, 2009). Therefore, klinotaxis allows C. elegans to learn how to orient correctly during navigation. Klinotaxis orientation is commonly linked with moving of sensors or its animal’s body through the environment; for example, a Drosophila larva moves the head laterally and uses olfactory organs to detect the gradient (Gomez-Marin et al., 2012). In gradient orientation, steering according to simultaneous comparisons of the stimulation by two distinct sense organs or bilateral sensors is known as tropotaxis (Martin, 1965). Vermiform animals use their sensors on the head and the tail for this strategy. Insects commonly use a pair of antennas as bilateral sensors to detect and ascend chemical gradients successfully to the source; this type of tropotaxis is named osmotropotaxis (Borst & Heisenberg, 1982; Flugge, 1934; Fraenkel & Guun, 1940; Kennedy, 1986; Martin, 1965; Otto, 1951; Schone, 1984). Adult fruit flies can turn to the side with a higher odor concentration by using osmotropotaxis strategy (Borst & Heisenberg, 1982; Duistermars, Chow, & Frye, 2009; Gaudry, Hong, Kain, de Bivort, & Wilson, 2013).

Chemotaxis also involves integration of information across sensory modalities, particularly at dynamic environments and/or distant sources. For instance, olfactory predators use olfactory cues to detect the presence of a prey and to get within a few meters of it. Once the prey’s general location has been determined, the predator may use a different modality such as vision to monitor an exact location. These olfactory predators include marine invertebrates and fish. In sharks, a lateral line lesion reduces the success rate in the ability to locate an odor source, but this deficiency only manifests in the dark (Gardiner & Atmea, 2007). This finding suggests that without visual inputs and lateral line information, olfactory inputs alone cannot support odor localization. It has also been suggested that Drosophila requires visual feedback to localize an odor source in flight (Frye et al., 2003). In many cases, vision is the most dominant secondary modality input to support chemotaxis.

Chemosensory tracking behavior can be executed by two possible mechanisms: sequential sampling and simultaneous sampling. In sequential sampling, the animal uses a single or few chemosensors to compare odor concentrations, one after the other, at two different spaces in the animal’s track. This mechanism involves spatial and temporal signal integration of subsequent samplings (Vickers, 2000). Klinotaxis is one of the mechanisms that reflect sequential sampling. In simultaneous sampling, the animal uses bilateral olfactory organs or two chemosensors on the animal’s body at the anterior–posterior axis to compare odor concentrations simultaneously. This mechanism may inform lateral differences of odor intensity and provide a basis for timing comparison (Catania, 2013; Gardiner & Atema, 2010; Gaudry et al., 2013; Porter et al., 2007; Rajan, Clement, & Bhalla, 2006; Takasaki, Namiki, & Kanzaki, 2012). Tropotaxis is one of the mechanisms that reflect simultaneous sampling.

Navigation in Complex and Dynamic Environments

Molecular diffusion models reliably describe chemotaxis in bacteria, microorganisms, and small crustaceans (Weissburg, 2000; Yen, Weissburg, & Doall, 1998). However, different models are used for dynamic and large-scale environments where turbulent (unsteady fluctuations) conditions are generated by the environment and the organisms. Volatile chemical molecules have no directional properties. Distribution on a surface such as the ground or dissolving of odors in air and liquids such as water generates a directional vector that can be detected by chemosensors. On the one hand, since molecular diffusion is slow, it operates in a small space (less than 1 mm), and decreases with distance. Disposition in a medium speeds up the carriage of the odors significantly. For example, air speed ups the odors >10³ times more than diffusion (Riffell et al., 2009); On the other hand, the medium creates chaotic spatiotemporal patterns. Therefore, spatiotemporal information of the stimulus that organisms use to navigate towards its source is highly dynamic and complex (Murlis & Jones, 1981).

Odor molecules spread out downwind in a plume and in water in a flume. A plume and a flume are distribution of chemicals with a sporadic structure generated by the interaction of flowing air or water with the odor source. Olfactory sensors of both invertebrates and vertebrates should be sensitive to the intermittent nature of the odor plume. One of the parameters that reflects this aspect of sensitivity is dynamic plasticity of the olfactory system. One of the evolutionary advantages of this plasticity is the continuous refinement of the olfactory system’s responses in order to optimize valuable environmental information (Stemmler & Koch, 1999).

Odor Source Localization in Aquatic Animals

Hydrodynamic stimuli are highly informative for orientation, hunting, and predator avoidance in aquatic environments. Hydrodynamic reception enables invertebrate and vertebrate marine animals to sense water movements generated by biotic sources such as predators, prey, or abiotic sources. This sensory system of mechano-reception is critically important for navigation. For instance, fish and sharks detect hydrodynamic stimuli by a lateral line sensory system. This consists of an array of sensors called neuromasts along the length of the fish’s body (Bleckmann, 1994; Coombs & Jansen, 1989). Many species of sharks use olfaction to locate their food (Gardiner & Atema, 2007); blocking their nostrils inhibits the orientation towards preys, and blocking one nostril leads to turning behavior towards the intact (Sheldon, 1911). Therefore, several studies have suggested that sharks may use tropotaxis behavior (Fraenkel & Gunn, 1940). Additionally, both invertebrate (such as crabs and fish) as well as vertebrate aquatic animals (such as sharks) may use the same mechanisms underlying odor source localization—specifically, simultaneous analysis of sensory inputs and hydrodynamic dispersal fields. Simultaneous sampling was shown to be used with both olfactory chemosensors and hydrodynamic sensors. In many cases, aquatic animals navigating odor flumes use the flow vector of a medium to locate the source of stimulation. The lemon shark, Negaprion brevirostris, swims upstream into the strongest current, without considering the chemical source location for its steering (Hodgson & Mathewson, 1971). This mechanism is characterized as “chemically stimulated rheotaxis.” Chemosensors and mechano-sensors are used for this rheotaxis behavior. A rheotaxic response in sharks also involves interplay between visual, olfactory, and mechano-receptive inputs (Gardiner & Atema, 2007). Gardiner and Atema demonstrated that with a lesioned lateral line system, most of the sharks could still orient to the mean flow and navigate to the upstream end of the flume; however, the presence of visible light was a critical factor for a successful outcome. They suggest that sharks compensated for the lack of lateral line information using the visual flow field for directional information. A beautiful example of odor navigation is exhibited by the lobster Homarus americanus, which can find odor sources 2 m away in turbulent odor plume conditions (Moore & Atema, 1991). During plume tracking, the lobsters walk at half their normal speed in an undulating path, in order to increase their tracking success without losing contact with the plume. The lobster uses an Eddy rheo-chemotaxis strategy (Atema, 1996). Eddy chemotaxis involves trail tracking in small-scale and odor-flavored turbulent environments. This process involves simultaneous detection of flavored eddies by chemo- and mechano-receptors. This strategy is highly informative since it includes the use of flavored eddies with the odor of the prey or food and water flow direction.

Surface-Borne Cues (Odor Tracking) Versus Airborne Cues (Odor Navigation)

Chemical stimuli can be deposited on firm surfaces to form trails; a scent trail on the ground is an example of surface-borne cues. Both invertebrates and vertebrates navigate in space to track an odor to its source by using surface-borne cues (Conover, 2007; Frye & Dickinson, 2004; Gardiner & Atema, 2007; Nevitt et al., 2008; Reidenbach & Koehl, 2011; Steck, Hansson, & Knaden, 2009). Ants are remarkable foragers that release pheromone trails on the ground to find their way back to the nest. Ants use their bilateral sensors, the antennae, to detect varying concentrations of the trail pheromone (Calenbuhr & Deneubourg, 1992; Hangartner, 1967). Hangartner studied the intact ant Lasius fuliginosus and showed that it uses an osmotropotaxis mechanism to measure odor concentration at two spatially separated antennae; crossing the left and the right antennae led to impairment in trail following (Hangartner, 1967).

German shepherd dogs follow the increasing concentration of odor by comparing the strength of odor intensities of sequential footprints (Steen & Wilsson, 1990). Thesen, Steen, and Doving investigated the olfactory tracking behavior of German shepherds by recording their sniffing activity during video-monitored trials (Thesen et al., 1993). The study demonstrates that either on the grass or on concrete, dogs needed to smell only two to five footprints to decide in which direction the track had been laid. The authors suggested that the dogs determine the track direction by perceiving a difference in the concentration of scent in the air above two consecutive prints. The authors found olfactory tracking behavior of the dogs divided into three phases: a searching phase, a decision-making phase, and a tracking phase. Humans are indeed able to perform some degree of scent tracking. Porter et al. demonstrated that blindfolded humans are capable of using only their noses to follow a 10 m-long scent trail in a crawl. Interestingly, accuracy in tracking decreased if they were deprived of bilateral nostril input (Porter et al., 2007). Additionally, human subject performance improved with training, measured by decreased deviation from the scent track with increased tracking velocity.

Yet another feature of the odor environment used by both invertebrates and vertebrates toward odor navigation is the directionality of airborne gradient cues traveling downwind from the source (Celani, Villermaux, & Vergassola, 2014). For instance, male moths fly upwind to track the reproductive pheromones released by female moths (David et al., 1983). This strategy is similar to the “chemically stimulated rheotaxis” behavior of aquatic animals; the moth first detects the presence of the odor and then uses the flow vector of the plume to steer towards the source of stimulation.

There are only a few studies to date that describe how mammals track airborne odors (Bhattacharyya & Bhalla, 2015; Catania, 2013; Gire, Kapoor, Arrighi-Allisan, Seminara, & Murthy, 2016). Gire et al. (2016) demonstrated that mice use airborne odor cues to navigate toward reward locations. Mice were trained to locate a water reward based on the nearby source of an airborne odor (with three chemically distinguished possible sources for each trial). The odors were dispersed into fluctuating plumes by turbulent airflow, and the intensity of odor signal was inversely proportional to the distance of the source. Trials were divided into a group close to the source (0–20 cm) and a group far from the source (40–60 cm). The study shows that mice are capable of navigating directly to odor sources by using airborne plumes. Interestingly, a gradient ascent algorithm was shown to be sufficient for a successful outcome without prior information. Moreover, the authors suggest that mice are capable of using previous experience to find reward sources faster and more effectively.

Pigeons’ remarkable ability to return home from unfamiliar locations can be explained, partially, by the use of airborne cues. Papi and colleagues discovered that sectioning the olfactory nerves of pigeons that were released at unfamiliar sites impaired their navigation back home (Papi, Fiore, Fiaschi, & Baldaccini, 1971; Papi, Fiore, Fiaschi, & Benvenuti, 1972), while anosmic pigeons released at familiar locations orient as well as intact birds (Benvenuti, Fiaschi, Fiore, & Papi, 1973). Following that discovery, several studies have since shown that homing pigeons find their way back home over hundreds of kilometers by using natural airborne volatiles (Wallraff, 2003, 2004, 2013, 2014). Wallraff and colleagues designed a research study aimed to examine whether a view of the horizon was critical for the pigeons’ navigation capability. Pigeons that were sheltered from the winds by glass screens were unable to orient towards their home. All together, these studies implied that pigeons at the home loft use the olfactory system and associate odors with wind direction for successful navigation. Pigeons have to use only stable airborne gradient molecules to determine terrestrial geographic locations (Wallraff, 2003, 2004, 2013, 2014). One of the hypotheses is that birds may use a cognitive map and coordinate system. The mechanisms underlying navigation in pigeons were suggested to involve the olfactory bulb as well as the hippocampus (Bingman et al., 2005; Jacobs & Menzel, 2014). Interestingly, recent findings indicate the significance of asymmetrical processing for odor navigation in pigeons; olfactory input occurring in the right piriform cortex (rPC) primarily activates the navigation circuitry of pigeons (Jorge, Marques, Pinto, & Phillips, 2016); the rPC is active only during the beginning of displacement, or initially at the release site, due to exposure to unfamiliar olfactory inputs. It has been suggested that the olfactory systems of many vertebrates, not just birds, map locations in space using odor gradients (Jacobs, 2012).

Stereo Olfaction in Mammals Versus Insects

Anatomy and Functionality of Odor Reception

The anatomical organization of the mammalian olfactory system appears to be fundamentally similar to that of the insect olfactory system (Brennan & Keverne, 1997; Haberly, 1998; Hildebrand & Shepherd, 1999; Laissue, Reiter, Hiesinger, Halter, & Fischbach, 1999; Laurent et al., 2001; Lessing & Carlson, 1999; Roman & Davis, 2001; Vosshall, Wong, & Axel, 2000). However, it is not clear if the mechanisms underlying odor localization are similar.

The olfactory receptor neurons (ORNs) serve as the interface between the animal’s surroundings and its nervous system. The ORNs of insects reside on the antennae and maxillary palps while the ORNs of mammals are inside the nose situated within a mucosa that is olfactory epithelium. The antennae and the maxillary palps are the primary organs that detect odors in insects, with the antennae densely covered with olfactory sensilla. The sensilla are in most cases hair-like structures with pores (de Bruyne & Baker, 2008). In insects, similar to the mammalian nose in which odorants have to pass the mucosa, odorants pass the sensillar lymph to reach the ORNs. Since the odor receptors of breathing mammals are located in the nose, there is a coupling of olfactory stimuli to their breathing cycle; therefore, they do not have continuous contact with the medium that contains the odors, and odor stimuli are discretized by the mammals’ sampling behavior (Macrides & Chorover, 1972). In contrast, insects’ olfactory organs are in direct contact to the medium, and odorants enter the lumen of the sensillum through pores. This is a notable difference between insect and mammal olfaction. Secondly, most insects have spatially separated antennae that allow them to sample their environment as it relates to these separated spatial coordinates. Additionally, many insects sweep their antennae repeatedly through odor fields to sample the environmental stimuli.

Mammals also have paired olfactory sensors (e.g., left and right nostrils). However, unlike the insects’ bilateral sensors, the terrestrial mammals’ nostrils are relatively close to one another and therefore provide little added resolution about spatially distinct information; for example, a rat’s nostrils are only approximately 3 millimeters apart (Rajan et al., 2006). An important distinction in mammalian olfaction is that it demonstrates passive as well as active sampling. Odors are made accessible through these two modes. Passive sampling is when an odor is carried within an airstream blown into the nostril. Odors in smaller trace quantities and/or possessing lower vapor pressure do not reach the olfactory mucosa as readily via passive diffusion, and are therefore detected via active sampling, commonly known as sniffing (Frasnelli, Charbonneau, Collignon, & Lepore, 2009). Sniffing has been shown to be important for odor detection, identification, and evaluation of ligand concentration via sensory intensity (Laing, 1983; Mainland & Sobel, 2006). Sniffing may also play a major role in olfactory perception (Bensafi et al., 2003; Mainland & Sobel, 2006; Sobel et al., 2000; Zelano et al., 2005) as well as in facilitation of odorant detection in humans (Sobel et al., 2000). Porter and colleagues have examined the correlation between sniffing and humans’ ability to follow a scent trail (Porter et al., 2007). They suggest that increasing tracking velocity requires an increase in sniffing frequency in order to get the same quality of olfactory information.

Therefore, fundamental differences of odor reception and odor sampling between insects and terrestrial vertebrates such as rodents are among the primary differences in the way the olfactory systems function.

Sequential and Simultaneous Sampling Underlying Odor Localization

Insects and mammals have both been shown to be sensitive to odor plumes far from their source. Insects detect an odor plume far more efficiently than the subsequent tracking phase toward its source than tracking. For instance, gypsy male moths can detect sexual pheromones at distances greater than 100 meters, yet ultimately it is a difficult task for them to find the female emitting them (David, Kennedy, & Ludlow, 1983; Elkinton, Schal, Ono, & Carde, 1987). Mammalian predators use a strategy in which they first detect the presence of an odor and then head directly upwind; if they can no longer find the scent of their prey, they may shift to a different strategy known as the “casting strategy,” moving back and forth lateral to the wind until they detect the odor again. Interestingly, zigzag movements are performed by both mammals and insects (David et al., 1983; Kanzaki, Sugi, & Shibuya, 1992; Kegnnedy, 1986; Khan, Sarangi, & Bhalla, 2012; Lent, Graham, & Collett, 2013; Porter et al., 2007; Vickers, 2000; Vickers & Baker, 1996; Willis & Avondet, 2005). The male silkmoth, Bombyx mori, uses multiple strategies: in response to a female sex pheromone, the male silkmoth moves upstream in straight-line bursts of walking until the pheromone is no longer detected, whereupon it uses zigzagging movements followed by a loop (Kanzaki et al., 1992). If the pheromones are detected again, the behavioral sequence is resumed with another surge (Kanzaki et al., 1992; Kramer, 1975). The nature of the interaction of sensory-motor coupling to localizing an odor source was examined by a silkmoth-driven mobile robot. Scientists from the University of Tokyo recently built a two-wheeled robot that was driven by female-seeking male silkmoths. The experimental setup included acquisition of olfactory information through two air suction tubes with air connectivity to the silkmoth. Additionally, the robot received visual information through a transparent canopy covering the cockpit. The scientists changed the odor gradient sampled by the bilateral sensors of the moth by changing the relative positions of the left and right air suction tubes gap (wide = 90 mm; narrow = 20 mm) to investigate the contribution of bilateral olfaction for odor source localization. Additionally, they crossed the air suction tube orientation to invert the olfactory inputs, and the control cables of the motors to invert the behavioral output. The results demonstrated a sequential approach in silkmoths, involving chemotactic surge and zigzagging strategies, which may be sufficient to localize an odor source even in the absence of accurate bilateral olfactory input.

The use of additional odor interrogation strategies, such as switching between serial and simultaneous sampling, has been reported in insects as well as mammals (Catania, 2013; Hangartner, 1967; Martin, 1965). It has been demonstrated that walking honeybees use both osmotropotaxis and klinotaxis mechanisms (Martin, 1965). Bees turn towards the side of the highest odor intensity as long as a concentration difference is sensed between the left and the right antennae. Bees with two antennae or one movable antenna can detect an odor source in a Y- maze. If one antenna is cut and the second is fixed, the bees can still detect the odor source by using a zigzag strategy. This suggests that bees may use sequential sampling. Moreover, crossing the left and the right antennae led to spatial disorientation and most bees turned towards the odorless branch of a Y-maze. This implies that bees compare the information across their two antennae. Martin also showed that if the tips of crossed antennae were fixed closer than 2 mm, there was a transition from osmotropotaxis to klinotaxis. The ability to follow odor gradients with only one sensor has similarly been demonstrated in ants. Intact ants compare sensory inputs by using their two sensors in order to stay on an odor trail (Hangartner, 1967). Crossing the antennae led to significant difficulty to track the odor trail. For Drosophila melanogaster it has been shown there is a tendency to turn toward the side of higher odor concentration with a corresponding circular track with a radius of 0.8 cm. Moreover, unilaterally antennectomized flies in a homogeneous odor field show a permanent turning tendency towards their intact side (Borst & Heisenberg, 1982).

A study was performed by Louis and colleagues (Louis, Huber, Benton, Sakmar, & Vosshall, 2008) to examine the importance of bilateral inputs for odor navigation in the larvae of Drosophila melanogaster. They established a structured airborne odor concentration gradient by using a small chamber whose ceiling (an inverted 96-well plate) suspended an ordered array of droplets of sequentially diluted odorants; this arrangement of droplets generated a spatial concentration distribution. In addition, they utilized transgenic unilateral larvae to study the contribution of bilateral chemoreception in odor navigation. Since the two olfactory sensors are so close together in fruit fly larvae, it seems unlikely that bilateral comparisons of odor gradients are important for successful navigation. The results indicated that fruit fly larvae can localize odor sources while only using unilateral inputs from a single functional sensory neuron. However, the authors found that fruit fly larvae with two sensors performed significantly better than those with one sensor when performing under complex odor environments, which are characterized by sharp odor gradients. They suggested that two distinct olfactory sensors may provide inputs with less noise correlation than inputs from a single receptor organ. Therefore, bilateral sensors may increase the signal-to-noise ratio in challenging environments.

In mammals, a study has revealed that blind, eastern American moles combine serial sampling with bilateral nasal cues to localize odorants (Catania, 2013). In this study, while the left or right nostril was blocked the mole was clearly biased to the side of the unblocked nostril, and search time to locate food was greatly increased compared with normal conditions. However, the moles did not turn in circles and were able to overcome the bias caused by the nostril block. Importantly, the results indicated the nostril block had its strongest effect close to the target, beginning at a distance of 4–5 cm. The authors suggest that internostril comparisons may be most informative nearby the odor source when the olfactory gradients have the steepest distribution. The crossing of the mole’s nostril impaired its search behavior, with the mole often missing the food completely. These important findings indicate that mammals can make use of stereo olfaction as well, which may be combined with serial sampling to localize an odor source.

Stereo Olfaction and Possible Mechanisms in Rodents

Mammals localize auditory sources by using simultaneous sampling across two ears. The differences in sound intensity and timing of the bilateral signal are converted to spatial coordinates. In the olfactory system, it has been commonly stressed that rodents are not able to receive spatially distinct information from their nostrils since the two olfactory sensors are too close to each other. As mentioned previously, rat nostrils are only about 3 mm apart (Rajan et al., 2006). The rodents’ main olfactory pathway is strongly ipsilateral. It begins in the periphery in the ORNs in the nose. Odorants are inhaled through the two nostrils into two nasal passages separated by the septum, and end their turbulent journey onto two olfactory epithelia. These epithelia are mirrored with regard to their arrangement of which ORNs species populate them. Therefore, odors inhaled through one nostril only activate ORNs of the corresponding olfactory epithelium on that same side of the septum (Kikuta et al., 2008). Sensory neurons project to the ipsilateral olfactory bulb (OB), and mitral and tufted output cells in the OB project their axons to the ipsilateral olfactory cortex (Mori et al., 1999). This includes the anterior olfactory nucleus (AON), piriform cortex (PCX), and entorhinal cortex. The AON receives input from both OBs. It receives excitatory inputs from the ipsilateral OB and from the contralateral olfactory cortex via the anterior commissure (Brunjes et al., 2005; De Carlos, Lopez-Mascaraque, & Valverde, 1989; Lei, Mooney, & Katz, 2006; Scott, Ranier, Pemberton, Orona, & Mouradian, 1985). Therefore, while the primary olfactory pathway is ipsilateral, there is an opportunity for interhemispheric information transfer. For example, olfactory memory has been shown to be accessible through odor exposure that is exclusively on either the left or right naris following unilateral odor training (Kucharski, Arnold, & Hall, 1995; Kucharski & Hall, 1987). Moreover, it has been demonstrated that functional connectivity between the bilateral anterior piriform cortices is learning‐ and context‐dependent (Cohen, Putrino, & Wilson, 2015; Cohen & Wilson, 2017). It has been revealed that olfactory information transfer between olfactory bulbs of mice may share odor identity information across hemispheres. This finding was suggested to be important for perceptual unity across hemispheres (Grobman et al., 2018). Interhemispheric information transfer may also support stereo odor localization and asymmetrical processing.

Rajan et al. suggested that rats use stereo cues such as internostril timing and intensity differences to localize odor sources (Rajan et al., 2006). This study used a behavioral conditioning paradigm of water-deprived rats trained to localize the source of an odor presented from the left or from the right. The rats actively initiated a trial by poking their nose into a sniff port. An odor stimulus was delivered on either the left or the right following a random interval of 0 to 100 milliseconds. This odor localization task was divided into four stages: nose poke, odor onset, nose withdrawal, and lick. The rat received a water reward if it licked the spout on the same side as the odor source. The sampling times and movement times were monitored. Importantly, the odor source was close to the animals. To answer the question if rats are using stereo cues to localize the source of the odor, Rajan et al. disrupted bilateral odor sampling by stitching one of the nostrils closed. Under these conditions the rats demonstrated poor performance, which recovered after the removal of the stitches. Additionally, similar to the results obtained in insects and moles (Borst & Heisenberg, 1982; Catania, 2013; Martin, 1965), the rats were also biased to the intact side. Importantly, few rats were trained to perform a forced choice task where the identity of the odor rather than the direction is the cue. The rats were trained to lick on the left water spout for the first odor and lick on the right water spout for the second one. This discrimination task between odors was not affected when one of the nostrils was stitched shut. Interestingly, while the forced choice task does not require directional detection ability by the two sensors, Cohen et al. revealed in two subsequent studies that asymmetrical plasticity in the PCX is correlated with this nondirectional task (Cohen et al., 2015; Cohen & Wilson, 2017). Finally, Rajan et al. used tetrodes to record single units in the main olfactory bulb. The recordings suggest that more than 90% of the responsive neurons in the olfactory bulb respond to odor direction. These responses may emerge due to the existence of feedback projections to the bulb, as well as reciprocal inhibitory projections from the contralateral bulb, through the AON. The importance of stereo olfaction in rodents is that odor location is significantly faster than sequential sampling. The speed with which odor sources are located may be evolutionarily important as both foraging and predator avoidance advantages; the ability to locate the direction of prey in one sniff rather than two sniffs was suggested to be critical to animal survival (Rajan et al., 2006).

As mentioned previously, the main interhemispheric connection of the rodent’s olfactory system is through the anterior commissure (AC), which originates on the AON (Jouandet & Hartenstein, 1983). Rabell et al. described a spontaneous and rapid odor source localization behavior, which depends on internostril odorant comparison (Rabell, Mutlu, Noutel, del Olmo, & Haesler, 2017). They performed a transection of the AC to demonstrate that the speed at which orienting toward the source of novel odorants is achieved in a single sniff involves interhemispheric communication. The transection of the AC eliminates nasal orienting toward novel smells. Additionally, unilateral AON lesions reverse orienting toward ipsilateral, but not contralateral, stimulation. Finally, by using an optogenetic technique, they found that unilateral activation of the AON triggered orienting towards the side of stimulation. Overall, this study suggests that rapid odor source localization behavior in mice depends on internostril odorant comparison and involves the AON.

The key role of single neurons in the lateral superior olive of cats is to compare ipsilateral and contralateral sound inputs of equivalent frequency (Tsuchitani & Boudreau, 1966). This function is essential to sound source localization. These neurons were shown to be sensitive to interaural intensity differences; specifically, they were excited by stimulation of the ipsilateral ear and suppressed by stimulation of the contralateral ear (Boudreau & Tsuchitani, 1968). Similarly, neurons in the AON pars externa (AONpE) of rats are involved in the localization of odor sources by processing the difference between ipsi-nostril and contra-nostril input signals of the same odor quality (Kikuta et al., 2010). Kikuta et al. suggested that AONpE neurons contribute to the localization of odor sources, either to the right or to the left side. They described this as ipsi-excitation and contra-inhibition (E-I) neurons. Each AONpE neuron demonstrated strong ipsi-nostril activation. In contrast, it indicated inhibitory responses by contra-nostril stimulation. Simultaneous odor stimulation of both nostrils generated a significantly smaller response compared with ipsi-nostril-only stimulation. Increasing the odor concentration of contra-nostril stimulation caused a larger suppression of the ipsi-nostril response. Overall, Kikuta and colleagues suggested that AONpE neurons are tuned to detect differences in concentration of odorants of a single category between ipsi- and contra-nostril inputs, and the E-I responses are generated by neuronal circuits within the AON itself.

Navigation Towards the Source Through Chemosensory Strategies and Mechanisms

Figure 2. Two possible pathways. Candidate neuronal pathways underlying right/left localization of odor sources. (a) One candidate pathway in which E-I-type responses are first generated in mitral/tufted (M/T) cells in the ipsilateral OB (ipsi-OB) and then transmitted to the ipsilateral AONpE. G, granule cells; AC, anterior commissure; (b) Another candidate pathway in which E-I-type responses are generated by neuronal circuits within the AON.

Reproduced from Kikuta et al. (2010).

A novel mechanism for odor localization in rodents is based on temporal input comparison. Parabucki and colleagues suggested that the ability of rodents to locate an odor source with one naris indicates temporal mode of comparison, based on odor concentration between sniffs (Δ‎Ct). They found that a subset of mitral/tufted (M/T) cells in the olfactory bulb may support this mechanism. Temporal comparison is likely executed by intra-bulbar circuits (Shepherd & Greer, 1998), or cortical feedback to the bulb rather than the inter-bulbar circuits underlying stereo olfaction described previously (Parabucki, Bizer, Morris, Smear, & Shusterman, 2017). Sniff-to-sniff comparison mechanisms may also play an important role in odor tracking behavior. While this research was performed with head-fixed mice, a recent study has shown that behaving mice are able to follow surface-borne trails following training by using sniff-to-sniff comparison (Jones & Urban, 2018). Jones and Urban have shown that mice use a casting strategy of back and forth movements across the odor trail. Unlike Parabucki’s study, which suggests that inter-sniff sequential sampling is sufficient for odor source localization in rodents, this study indicates that mice use both rapid sniff-by-sniff comparisons of odor strength and stereo olfaction as well. The differences in the intensity between the current sniff and the previous one is an important distinguisher to perform odor tracking behavior. The mice responded to intensity changes rapidly, within approximately 80 milliseconds. Unilateral naris occlusion indicated the importance of bilateral sensory information for this task. Occlusion significantly impaired the efficiency with which the mice followed the trail. These results suggest that rodents compare odor magnitude arriving at each of the bilateral sensors nares within a single sniff. Importantly, this strategy is particularly valuable when mice are close to an odor trail.

Discussion

In this article I summarized two basic mechanisms for odor navigation: simultaneous sampling, based on differences across two sensors that sample time and concentration differences; and sequential sampling, based on one or more chemosensors evaluating concentration differences between samples one after the other at two distinct coordinates. Both strategies are based on spatial and/or temporal characterizations. Various studies on odor source location in dynamic and complex environments indicate that both invertebrates and vertebrates use a diversity of strategies to navigate towards chemical gradient sources. In some cases they shift between sequential and simultaneous sampling or between random and directed movements (Catania, 2013; Hangartner, 1967; Martin, 1965). They may also use an interplay of diverse sensory modalities—in particular the visual system (Frye et al., 2003; Gardiner & Atmea, 2007). Additionally, animals utilize the medium’s flow vector of either wind or water to locate the source of an odor plume. Marine animals use mechano-reception systems for computation of hydrodynamic stimuli. The interplay between visual, olfactory (either bilateral or unilateral), and mechano-receptive inputs may be critical for odor source navigation. The role of mechano-reception in odor navigation should also be considered in rodents. The lengthened tactile hairs (whiskers) on the snouts of nocturnally active mammals such as rats and mice form a vibrissae sensory array that senses objects in the surrounding area of the animal’s body (Ahl, 1986). One study suggests that the vibrissae sensory array is mechanically sensitive to airflow. Moreover, rodents could actively adjust how the vibrissae respond to airflow by changing the orientation of the whiskers (Yan et al., 2016). Therefore, as is the case for aquatic mammals and insect flies, terrestrial mammals may use mechano-reception to move upwind upon encounter with an odor toward its source localization. This potential contribution of odor source localization to research in rodent olfaction should be accounted for in future studies.

A particular focus of this article is to underline the differences between insects and mammals in regards to the role of stereo olfaction in odor source localization. Studies of several mammals have shown that stereo olfaction is used to navigate towards odor sources and to track odor trails (Catania, 2013; Khan et al., 2012; Porter et al., 2007; Rabell et al., 2017; Rajan et al., 2006). However, those studies and others demonstrate that mammals can still localize and track odors successfully without using stereo olfaction, although the performance is impaired. The ability to follow odor gradients with only a unilateral sensor has also been demonstrated in bees, sharks, humans, fly larvae, and ants (Hangartner, 1967; Louis et al., 2008; Martin, 1965; Porter at al., 2007; Sheldon, 1911). Invertebrates and vertebrates rely on a unilateral sensor by moving their body or their sensor along the path toward the source. By using sequential sampling, they compare olfactory concentrations over time and may also use a casting behavior—a periodic, side-to-side movement (Kennedy, 1986). Overall, those studies strongly indicate that one olfactory sensor is sufficient for odor source localization. Therefore, the role of stereo olfaction is puzzling. Is there any significant advantage for bilateral sensors versus a unilateral sensor? On the one hand, recent studies in moles, rodents, and humans suggest that stereo olfaction is essential (Catania, 2013; Porter et al., 2007; Rajan et al., 2006). Stereo olfaction may be facilitated by directional neurons in the AON (Kikuta et al., 2010). On the other hand, animals can still find odor sources and follow odor trails with one naris blocked. In rodents, one of the optional mechanisms for a successful outcome is based on temporal comparison of odor concentration, from sniff to sniff (Parabucki et al., 2017).

The first suggestion of this article is that stereo olfaction may be important for terrestrial animals for tracking mainly nearby odor sources. The chemical gradient is steep proximate to odor sources, and therefore is highly informative for proximate bilateral sensors. The second suggestion is the importance of mechano-reception for odor source localization in rodents, as has been demonstrated in marine mammals. The third suggestion is the involvement of a top-down pathway (for instance the PCX-OB pathway) for rodents to locate an odor source. Since odor stimuli are discretized by the mammals’ sampling behavior and each sniff represents an autonomous event, higher brain regions must compare the previous memory of odor concentration with the current memory. Interestingly, the importance of asymmetrical processing in the olfactory cortical system of rodents has been revealed (Cohen et al., 2015; Cohen & Wilson, 2017); this asymmetrical plasticity was suggested to be important for olfactory learning and memory. Cortical asymmetrical processing may also be involved in stereo olfaction.

To summarize, animals use sophisticated behavioral strategies and sensory systems to navigate towards odor sources. Mammals may smell in stereo to significantly reduce the time required to locate an odor source. This approach provides instantaneous information for both foraging and predator avoidance. In particular, stereo olfaction is beneficial for nearby odor sources where odor gradients are steep, since the sensors are close together. The visual system also has an important role for odor source localization in invertebrates and vertebrates. Similar to the auditory system, one possible mechanism underlying odor source localization involves the inter-bulbar circuitry across hemispheres through the AON. In other cases, mammals also use temporal comparison by a unilateral sensor. This mechanism may involve a temporal sniff-to-sniff strategy, and is probably executed by intra-bulbar circuits or cortical feedback to the bulb. Recently, the principles of animal navigation were adapted by biomimetic engineering of autonomous robots that mimic the physiological mechanisms underlying odor source localization, particularly in dynamic environments (Benhamou & Bovet, 1989; Franz & Mallot, 2000).

Acknowledgments

I thank my wife Angela Cohen, Dr. Ben Sadrian, and Dr. Iris Reuveni for their comments on the manuscript.

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