Sensory coding of pheromone signals in mammals

The vomeronasal organ (VNO) of mammals plays an essential role in the detection of pheromones, chemical cues secreted by animals that elicit genetically programmed sexual and aggressive behaviors among conspecifics. The recent characterization of genes encoding molecular components of the VNO sensory response suggests that VNO neurons express a unique set of molecules to recognize and translate pheromone signals into neuronal electrical activity. Identification of these genes, which include putative pheromone receptor genes, has offered a new opportunity to uncover basic principles of pheromone sensory processing and important aspects of vomeronasal development.     

Odor coding in the maxillary palp of the malaria vector mosquito Anopheles gambiae

BACKGROUND: Many species of mosquitoes, including the major malaria vector Anopheles gambiae, utilize carbon dioxide (CO(2)) and 1-octen-3-ol as olfactory cues in host-seeking behaviors that underlie their vectorial capacity. However, the molecular and cellular basis of such olfactory responses remains largely unknown. RESULTS: Here, we use molecular and physiological approaches coupled with systematic functional analyses to define the complete olfactory sensory map of the An. gambiae maxillary palp, an olfactory appendage that mediates the detection of these compounds. In doing so, we identify three olfactory receptor neurons (ORNs) that are organized in stereotyped triads within the maxillary-palp capitate-peg-sensillum population. One ORN is CO(2)-responsive and characterized by the coexpression of three receptors that confer CO(2) responses, whereas the other ORNs express characteristic odorant receptors (AgORs) that are responsible for their in vivo olfactory responses. CONCLUSIONS: Our results describe a complete and highly concordant map of both the molecular and cellular olfactory components on the maxillary palp of the adult female An. gambiae mosquito. These results also facilitate the understanding of how An. gambiae mosquitoes sense olfactory cues that might be exploited to compromise their ability to transmit malaria.     

Responses to innocuous, but not noxious, somatosensory stimulation by neurons in the ferret superior colliculus

The intermediate and deep layers of the superior colliculus (SC) are known for their role in initiating orienting behaviors. To direct these orienting functions, the SC of some animals (e.g., primates, carnivores) is dominated by inputs from the distance senses (vision, audition). In contrast, the rodent SC relies more heavily on non-visual inputs, such as touch and nociception, possibly as an adaptive response to the proximity of dangers encountered during their somatosensory-dominant search behaviors. The ferret (a carnivore) seems to employ strategies of both groups: above ground they use visual/auditory cues, but during subterranean hunting ferrets must rely on non-visual signals to direct orienting. Therefore, the present experiments sought to determine whether the sensory inputs to the ferret SC reveal adaptations common to functioning in both environments. The results showed that the ferret SC is dominated (63%; 181/286) by visual/auditory inputs (like the cat), rather than by somatosensory inputs (as found in rodents). Furthermore, tactile responses were driven primarily from hair-receptors (like cats), not from the vibrissae (as in rodents). Additionally, while a majority of collicular neurons in rodents respond to brief noxious stimulation, no such neurons were encountered in the ferret SC. A small proportion (4%; 13/286) of the ferret SC neurons were responsive to long-duration (>5 s) noxious stimulation, but further tests could not establish these responses as nociceptive. Collectively, these data indicate that the ferret SC is best adapted for the animal's visuallacoustically guided activities and most closely resembles the SC of its phylogenetic relative, the cat.     

Responses to innocuous,but not noxious,somatosensory stimulation by neurons in the ferret superior colliculus

The intermediate and deep layers of the superior colliculus (SC) are known for their role in initiating orienting behaviors. To direct these orienting functions, the SC of some animals (e.g., primates, carnivores) is dominated by inputs from the distance senses (vision, audition). In contrast, the rodent SC relies more heavily on non-visual inputs, such as touch and nociception, possibly as an adaptive response to the proximity of dangers encountered during their somatosensory-dominant search behaviors. The ferret (a carnivore) seems to employ strategies of both groups: above ground they use visual/auditory cues, but during subterranean hunting ferrets must rely on non-visual signals to direct orienting. Therefore, the present experiments sought to determine whether the sensory inputs to the ferret SC reveal adaptations common to functioning in both environments. The results showed that the ferret SC is dominated (63%; 181/286) by visual/auditory inputs (like the cat), rather than by somatosensory inputs (as found in rodents). Furthermore, tactile responses were driven primarily from hair-receptors (like cats), not from the vibrissae (as in rodents). Additionally, while a majority of collicular neurons in rodents respond to brief noxious stimulation, no such neurons were encountered in the ferret SC. A small proportion (4%; 13/286) of the ferret SC neurons were responsive to long-duration (> 5s) noxious stimulation, but further tests could not establish these responses as nociceptive. Collectively, these data indicate that the ferret SC is best adapted for the animal's visual/acoustically guided activities and most closely resembles the SC of its phylogenetic relative, the cat.     

Functional specialization of mouse higher visual cortical areas

The mouse is emerging as an important model for understanding how sensory neocortex extracts cues to guide behavior, yet little is known about how these cues are processed beyond primary cortical areas. Here, we used two-photon calcium imaging in awake mice to compare visual responses in primary visual cortex (V1) and in two downstream target areas, AL and PM. Neighboring V1 neurons had diverse stimulus preferences spanning five octaves in spatial and temporal frequency. By contrast, AL and PM neurons responded best to distinct ranges of stimulus parameters. Most strikingly, AL neurons preferred fast-moving stimuli while PM neurons preferred slow-moving stimuli. By contrast, neurons in V1, AL, and PM demonstrated similar selectivity for stimulus orientation but not for stimulus direction. Based on these findings, we predict that area AL helps guide behaviors involving fast-moving stimuli (e.g., optic flow), while area PM?helps guide behaviors involving slow-moving objects.     

Smelling on the fly: sensory cues and strategies for olfactory navigation in Drosophila

Navigating toward (or away from) a remote odor source is a challenging problem that requires integrating olfactory information with visual and mechanosensory cues. Drosophila melanogaster is a useful organism for studying the neural mechanisms of these navigation behaviors. There are a wealth of genetic tools in this organism, as well as a history of inventive behavioral experiments. There is also a large and growing literature in Drosophila on the neural coding of olfactory, visual, and mechanosensory stimuli. Here we review recent progress in understanding how these stimulus modalities are encoded in the Drosophila nervous system. We also discuss what strategies a fly might use to navigate in a natural olfactory landscape while making use of all these sources of sensory information. We emphasize that Drosophila are likely to switch between multiple strategies for olfactory navigation, depending on the availability of various sensory cues. Finally, we highlight future research directions that will be important in understanding the neural circuits that underlie these behaviors.     

The neurobiology of sensing respiratory gases for the control of animal behavior

Aerobic metabolism is fundamental for almost all animal life.Cellular consumption of oxygen (O2) and production of carbon dioxide (CO2) signal metabolic states and physiologic stresses.These respirator...     

Dopaminergic modulation of sucrose acceptance behavior in Drosophila

For an animal to survive in a constantly changing environment, its behavior must be shaped by the complex milieu of sensory stimuli it detects, its previous experience, and its internal state. Although taste behaviors in the fly are relatively simple, with sugars eliciting acceptance behavior and bitter compounds avoidance, these behaviors are also plastic and are modified by intrinsic and extrinsic cues, such as hunger and sensory stimuli. Here, we show that dopamine modulates a simple taste behavior, proboscis extension to sucrose. Conditional silencing of dopaminergic neurons reduces proboscis extension probability, and increased activation of dopaminergic neurons increases extension to sucrose, but not to bitter compounds or water. One dopaminergic neuron with extensive branching in the primary taste relay, the subesophageal ganglion, triggers proboscis extension, and its activity is altered by satiety state. These studies demonstrate the marked specificity of dopamine signaling and provide a foundation to examine neural mechanisms of feeding modulation in the fly.     

A sensory code for host seeking in parasitic nematodes

Parasitic nematode species often display highly specialized host-seeking behaviors that reflect their specific host preferences. Many such behaviors are triggered by host odors, but little is known about either the specific olfactory cues that trigger these behaviors or the underlying neural circuits. Heterorhabditis bacteriophora and Steinernema carpocapsae are phylogenetically distant insect-parasitic nematodes whose host-seeking and host-invasion behavior resembles that of some devastating human- and plant-parasitic nematodes. We compare the olfactory responses of Heterorhabditis and Steinernema infective juveniles (IJs) to those of Caenorhabditis elegans dauers, which are analogous life stages. The broad host range of these parasites results from their ability to respond to the universally produced signal carbon dioxide (CO(2)), as well as a wide array of odors, including host-specific odors that we identified using thermal desorption-gas chromatography-mass spectroscopy. We find that CO(2) is attractive for the parasitic IJs and C. elegans dauers despite being repulsive for C. elegans adults, and we identify a sensory neuron that mediates CO(2) response in both parasitic and free-living species, regardless of whether CO(2) is attractive or repulsive. The parasites' odor response profiles are more similar to each other than to that of C. elegans despite their greater phylogenetic distance, likely reflecting evolutionary convergence to insect parasitism.     

Neurally Encoding Time for Olfactory Navigation

Accurately encoding time is one of the fundamental challenges faced by the nervous system in mediating behavior. We recently reported that some animals have a specialized population of rhythmically active neurons in their olfactory organs with the potential to peripherally encode temporal information about odor encounters. If these neurons do indeed encode the timing of odor arrivals, it should be possible to demonstrate that this capacity has some functional significance. Here we show how this sensory input can profoundly influence an animal’s ability to locate the source of odor cues in realistic turbulent environments—a common task faced by species that rely on olfactory cues for navigation. Using detailed data from a turbulent plume created in the laboratory, we reconstruct the spatiotemporal behavior of a real odor field. We use recurrence theory to show that information about position relative to the source of the odor plume is embedded in the timing between odor pulses. Then, using a parameterized computational model, we show how an animal can use populations of rhythmically active neurons to capture and encode this temporal information in real time, and use it to efficiently navigate to an odor source. Our results demonstrate that the capacity to accurately encode temporal information about sensory cues may be crucial for efficient olfactory navigation. More generally, our results suggest a mechanism for extracting and encoding temporal information from the sensory environment that could have broad utility for neural information processing.     

Temperature, oxygen, and salt-sensing neurons in C. elegans are carbon dioxide sensors that control avoidance behavior

Homeostatic control of body fluid CO(2) is essential in animals but is poorly understood. C.?elegans relies on diffusion for gas exchange and avoids environments with elevated CO(2). We show that C.?elegans temperature, O(2), and salt-sensing neurons are also CO(2) sensors mediating CO(2) avoidance. AFD thermosensors respond to increasing CO(2) by a fall and then rise in Ca(2+) and show a Ca(2+) spike when CO(2) decreases. BAG O(2) sensors and ASE salt sensors are both activated by CO(2) and remain tonically active while high CO(2) persists. CO(2)-evoked Ca(2+) responses in AFD and BAG neurons require cGMP-gated ion channels. Atypical soluble guanylate cyclases mediating O(2) responses also contribute to BAG CO(2) responses. AFD and BAG neurons together stimulate turning when CO(2) rises and inhibit turning when CO(2) falls. Our results show that C.?elegans senses CO(2) using functionally diverse sensory neurons acting homeostatically to minimize exposure to elevated CO(2).     

Cautious cannibals: Behavioral responses of juvenile and adult blue crabs to the odor of injured conspecifics

Blue crabs are cannibalistic, and therefore the scent of injured conspecifics represents both a potential food cue, as well as an indicator of predation risk. We examined the response of blue crabs to conspecific odor alone, as well as in mixtures of attractive cues to determine how animals evaluate and respond to this odor. We explicitly manipulated risk-sensitivity based on either animal size (an indicator of susceptibility to predation) or hunger state (susceptibility to starvation) as ways to evaluate theories of risk-allocation, which suggest that decreases in predation risk, or increases in the risk of starvation, ought to result in diminished responses to sensory cues that signal predator presence or activity. Large and small blue crabs were challenged to locate the source of odor plumes consisting of the scent of injured conspecifics (risk cue), attractive food odors (attractive cue), or their mixture (conflicting cue). Neither large nor small blue crabs tracked aversive cues, but large blue crabs consistently tracked conflicting treatments to their source. Responses to conflicting and aversive treatments also involved diminished movement and reduced tracking speed relative to behaviors displayed in attractive plumes. Thus, even cannibalistic crabs seem to respond more prevalently to the apparent predation risk then to food reward, and risk-sensitive behaviors have a likely cost in terms of reduced food intake. Starved animals were more likely than unstarved animals to track conflicting plumes. Both the ontogenic shift and the response of starved animals support the notion that the cost of risk-aversive behaviors results in this strategy being allocated in proportion to the degree of potential risk. Since risk-aversive responses to chemical cues can produce strong effects in communities, the size-dependent nature of these responses in blue crabs may introduce considerable complexity in interactions between blue crabs, their predators, and their prey.     

Understanding the regulation and function of adult neurogenesis: contribution from an insect model, the house cricket

Since the discovery of adult neurogenesis, a major issue is the role of newborn neurons and the function-dependent regulation of adult neurogenesis. We decided to use an animal model with a relatively simple brain to address these questions. In the adult cricket brain as in mammals, new neurons are produced throughout life. This neurogenesis occurs in the main integrative centers of the insect brain, the mushroom bodies (MBs), where the neuroblasts responsible for their formation persist after the imaginal molt. The rate of production of new neurons is controlled not only by internal cues such as morphogenetic hormones but also by external environmental cues. Adult crickets reared in an enriched sensory environment experienced an increase in neuroblast proliferation as compared with crickets reared in an impoverished environment. In addition, unilateral sensory deprivation led to reduced neurogenesis in the MB ipsilateral to the lesion. In search of a functional role for the new cells, we specifically ablated MB neuroblasts in young adults using brain-focused gamma ray irradiation. We developed a learning paradigm adapted to the cricket, which we call the "escape paradigm." Using this operant associative learning test, we showed that crickets lacking neurogenesis exhibited delayed learning and reduced memory retention of the task when olfactory cues were used. Our results suggest that environmental cues are able to influence adult neurogenesis and that, in turn, newly generated neurons participate in olfactory integration, optimizing learning abilities of the animal, and thus its adaptation to its environment. Nevertheless, odor learning in adult insects cannot always be attributed to newly born neurons because neurogenesis is completed earlier in development in many insect species. In addition, many of the irradiated crickets performed significantly better than chance on the operant learning task.     

Sensory System Affects Orientational Strategy in a Short-Range Spatial Task in Blind and Eyed Morphs of the Fish, Astyanax fasciatus

In the concerted effort to discover the mechanisms that animals use to orient through space, little attention has been given to the role of the sensory system on shaping orientational strategy. This study tests whether animals with different sensory systems use different mechanisms to orient. The characin fish Astyanax fasciatus (Cuvier, 1819) exists in two morphs in the same species – a number of populations of blind cave fish that rely on their lateral line to gain fine-scale information from their surroundings, and eyed surface populations that can also use visual cues. Both forms of the species were trained to orient to a goal signalled by landmarks and by egocentrically based cues (turn left or right) in a T-maze. When these cues were placed in conflict by switching the landmark position, only the eyed fish used the landmarks to orient, reflecting a difference in the way that the two sensory systems of these animals operate. Our results have implications for the evolution of the mechanisms of orientation, suggesting that these mechanisms may be constrained by the sensory cues that are available and hence the type of information that animals are able to glean from their surroundings.     

Encoding olfactory signals via multiple chemosensory systems

Most animals have evolved multiple olfactory systems to detect general odors as well as social cues. The sophistication and interaction of these systems permit precise detection of food, danger, and mates, all crucial elements for survival. In most mammals, the nose contains two well described chemosensory apparatuses (the main olfactory epithelium and the vomeronasal organ), each of which comprises several subtypes of sensory neurons expressing distinct receptors and signal transduction machineries. In many species (e.g., rodents), the nasal cavity also includes two spatially segregated clusters of neurons forming the septal organ of Masera and the Grueneberg ganglion. Results of recent studies suggest that these chemosensory systems perceive diverse but overlapping olfactory cues and that some neurons may even detect the pressure changes carried by the airflow. This review provides an update on how chemosensory neurons transduce chemical (and possibly mechanical) stimuli into electrical signals, and what information each system brings into the brain. Future investigation will focus on the specific ligands that each system detects with a behavioral context and the processing networks that each system involves in the brain. Such studies will lead to a better understanding of how the multiple olfactory systems, acting in concert, offer a complete representation of the chemical world.     

Light activation of an innate olfactory avoidance response in Drosophila

How specific sensory stimuli evoke specific behaviors is a fundamental problem in neurobiology. In Drosophila, most odorants elicit attraction or avoidance depending on their concentration, as well as their identity [1]. Such odorants, moreover, typically activate combinations of glomeruli in the antennal lobe of the brain [2-4], complicating the dissection of the circuits translating odor recognition into behavior. Carbon dioxide (CO2), in contrast, elicits avoidance over a wide range of concentrations [5, 6] and activates only a single glomerulus, V [5]. The V glomerulus receives projections from olfactory receptor neurons (ORNs) that coexpress two GPCRs, Gr21a and Gr63a, that together comprise a CO2 receptor [7-9]. These CO2-sensitive ORNs, located in the ab1 sensilla of the antenna, are called ab1c neurons [10]. Genetic silencing of ab1c neurons indicates that they are necessary for CO2-avoidance behavior [5]. Whether activation of these neurons alone is sufficient to elicit this behavior, or whether CO2 avoidance requires additional inputs (e.g., from the respiratory system), remains unclear. Here, we show that artificial stimulation of ab1c neurons with light (normally attractive to flies) elicits the avoidance behavior typical of CO2. Thus, avoidance behavior appears hardwired into the olfactory circuitry that detects CO2 in Drosophila.     

Contextual taste cues modulate olfactory learning in C. elegans by an occasion-setting mechanism

Manipulations of context can affect learning and memory performance across species in many associative learning paradigms. Using taste cues to create distinct contexts for olfactory adaptation assays in the nematode Caenorhabditis elegans, we now show that performance in this associative learning paradigm is sensitive to context manipulations, and we investigate the mechanism(s) used for the integration of context cues in learning. One possibility is that the taste and olfactory stimuli are perceived as a combined, blended cue that the animals then associate with the unconditioned stimulus (US) in the same manner as with any other unitary conditioned stimuli (CS). Alternatively, an occasion-setting model suggests that the taste cues only define the appropriate context for olfactory memory retrieval without directly entering into the primary association. Analysis of genetic mutants demonstrated that the olfactory and context cues are sensed by distinct primary sensory neurons and that the animals' ability to use taste cues to modulate olfactory learning is independent from their ability to utilize these same taste cues for adaptation. We interpret these results as evidence for the occasion-setting mechanism in which context cues modulate primary Pavlovian association by functioning in a hierarchical manner to define the appropriate setting for memory recall.     

Altered sensory projections in the chick hind limb following the early removal of motoneurons

Chick sensory neurons grow to their correct targets in the hindlimb from the outset during normal development and following various experimental manipulations. This may result not because sensory neurons respond to specific limb-derived cues, but because they interact in some way with motoneurons which are responsive to such cues. To test this possibility, we removed the ventral part of the neural tube, which contains motoneurons and their precursors, at stages 16 1/2-20 1/2 and later examined the pathways sensory neurons had taken within the limb. Muscle nerves generally were missing or were reduced in diameter beyond the extent expected simply from the absence of motoneuron axons. In many cases, cutaneous nerves were enlarged, presumably due to the addition of other sensory axons. This result suggests that, in the absence of motoneurons, sensory neurons that normally project to muscles are unable to do so and may instead project along cutaneous pathways. Sensory axons from different segments also crossed less extensively in the plexus region than they did in control embryos, suggesting that alterations in their trajectories may normally be facilitated by similar changes in motoneuron pathways. Thus, motoneurons greatly enhance sensory neuron growth to muscles and contribute significantly toward the achievement of the normal sensory projection pattern. Sensory axons may fasciculate with motoneuron axons, or motoneuron axons may provide an aligned substrate for sensory neurons to grow along. Alternatively, motoneuron axons may alter the environment, thereby making certain pathways in the limb permissive for sensory neuron growth.     

Building neural choice points for love and war

The molecular specification of central circuits that coordinate expression of innate behaviors in response to specific sensory cues from the environment remains a puzzle. In this issue of Neuron, Choi, Dong, and colleagues used expression profiling and genetic axonal tracing to visualize a hypothalamic point of convergence for defensive and reproductive olfactory cues that may function as a gating mechanism for sensory activation of defensive responses over reproduction.     

New oral linguiform projections and their associated neurons in the third-stage infective larva of the parasitic nematode Oesophagostomum dentatum

The infective larvae (L3i) of the nematode parasite of swine, Oesophagostomum dentatum, are passively ingested by their hosts. The L3i exhibit certain behaviors that are probably selected to increase the likelihood of ingestion, by strategic positioning in the environment. The larvae show positive geotactic behavior and respond to temperature variations in their environment, as shown by their behavior on a thermal gradient. To investigate neuronal control of this behavior, we initiated a study of the structure of the amphidial neurons of this parasite. The same number and types of neuronal dendritic processes are found in the amphids of the O. dentatum L3i as in those of its close relatives Haemonchus contortus and Ancylostoma caninum. Well-developed dendritic processes of wing cells are located in the amphidial sheath cells, these being similar to wing cells AWA in the free-living nematode Caenorhabditis elegans but actually more extensive. Similar to its close relatives just mentioned, and C. elegans as well, O. dentatum L3i has prominent finger cell processes, the finger cell neurons being the thermoreceptors in all 3 of the preceding species. However, unlike the arrangement seen in H. contortus and A. caninum, where the microvilli-like "fingers" of these neurons lie dorsal to the amphidial channel and occupy a very large portion (>50%) of the anterior end of the larva, the dendritic process of the finger cells in O. dentatum extends into unusual linguiform projections that, in turn, extend into the lumen of the mouth tube, a complex structural arrangement that has not been described for any other nematode.