Differential combinatorial coding of pheromones in two olfactory subsystems of the honey bee brain.

Neural coding of pheromones has been intensively studied in insects with a particular focus on sex pheromones. These studies favored the view that pheromone compounds are processed within specific antennal lobe glomeruli following a specialized labeled-line system. However, pheromones play crucial roles in an insect's life beyond sexual attraction, and some species use many different pheromones making such a labeled-line organization unrealistic. A combinatorial coding scheme, in which each component activates a set of broadly tuned units, appears more adapted in this case. However, this idea has not been tested thoroughly. We focused here on the honey bee Apis mellifera, a social insect that relies on a wide range of pheromones to ensure colony cohesion. Interestingly, the honey bee olfactory system harbors two central parallel pathways, whose functions remain largely unknown. Using optophysiological recordings of projection neurons, we compared the responses of these two pathways to 27 known honey bee pheromonal compounds emitted by the brood, the workers, and the queen. We show that while queen mandibular pheromone is processed by l-ALT (lateral antennal lobe tract) neurons and brood pheromone is mainly processed by m-ALT (median antennal lobe tract) neurons, worker pheromones induce redundant activity in both pathways. Moreover, all tested pheromonal compounds induce combinatorial activity from several AL glomeruli. These findings support the combinatorial coding scheme and suggest that higher-order brain centers reading out these combinatorial activity patterns may eventually classify olfactory signals according to their biological meaning.

Potential effects of pleasant and cold stimuli on nausea and vomiting induced by disgusting tastes.

Several pharmacological agents have disgusting tastes that are perceived strongly in the back of the mouth and may trigger nausea and vomiting (NV), resulting in poor adherence to medication schedules and negative impacts on clinical outcomes. Pleasant stimuli and cold temperature lessen the disgusting stimuli, lowering NV through different mechanisms. A pleasant stimulus can mask an unpleasant one, presumably through lateral inhibitory connections in the local neuronal circuit. Similarly, temperature deeply influences taste perception because the response to bitter as well as to salty and sour has been found to assume a reversed U-shaped form, being reduced by cooling to 18°C and enhanced by warming to 30-37°C. This Review describes the mechanisms by which pleasant and cold stimuli may mask emetogenic disgusting stimuli and identifies the potential clinical applications of cooling for inhibiting objectionable drug-related gustatory reactions. © 2015 Wiley Periodicals, Inc.

Comparative analysis of deutocerebral neuropils in Chilopoda (Myriapoda): implications for the evolution of the arthropod olfactory system and support for the Mandibulata concept.

BACKGROUND: Originating from a marine ancestor, the myriapods most likely invaded land independently of the hexapods. As these two evolutionary lineages conquered land in parallel but separately, we are interested in comparing the myriapod chemosensory system to that of hexapods to gain insights into possible adaptations for olfaction in air. Our study connects to a previous analysis of the brain and behavior of the chilopod (centipede) Scutigera coleoptrata in which we demonstrated that these animals do respond to volatile substances and analyzed the structure of their central olfactory pathway. RESULTS: Here, we examined the architecture of the deutocerebral brain areas (which process input from the antennae) in seven additional representatives of the Chilopoda, covering all major subtaxa, by histology, confocal laser-scan microscopy, and 3D reconstruction. We found that in all species that we studied the majority of antennal afferents target two separate neuropils, the olfactory lobe (chemosensory, composed of glomerular neuropil compartments) and the corpus lamellosum (mechanosensory). The numbers of olfactory glomeruli in the different chilopod taxa ranged from ca. 35 up to ca. 90 and the shape of the glomeruli ranged from spheroid across ovoid or drop-shape to elongate. CONCLUSION: A split of the afferents from the (first) pair of antennae into separate chemosensory and mechanosensory components is also typical for Crustacea and Hexapoda, but this set of characters is absent in Chelicerata. We suggest that this character set strongly supports the Mandibulata hypothesis (Myriapoda + (Crustacea + Hexapoda)) as opposed to the Myriochelata concept (Myriapoda + Chelicerata). The evolutionary implications of our findings, particularly the plasticity of glomerular shape, are discussed.

Taste, olfactory and food texture reward processing in the brain and obesity.

Complementary neuronal recordings and functional neuroimaging in humans, show that the primary taste cortex in the anterior insula provides separate and combined representations of the taste, temperature and texture (including fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex (OFC), these sensory inputs are for some neurons combined by learning with olfactory and visual inputs, and these neurons encode food reward in that they only respond to food when hungry, and in that activations correlate with subjective pleasantness. Cognitive factors, including word-level descriptions, and attention, modulate the representation of the reward value of food in the OFC. Further, there are individual differences in the representation of the reward value of food in the OFC. It is argued that overeating and obesity are related in many cases to an increased reward value of the sensory inputs produced by foods, and their modulation by cognition and attention, which overrides existing satiety signals. It is proposed that control of all rather than one or several of these factors that influence food reward and eating may be important in the prevention and treatment of overeating and obesity.

A truffle in the mouth is worth two in the bush: odor localization in the human brain.

It is widely thought that locating the source of a smell is an ability best left to nonhuman members of the animal kingdom. In this issue of Neuron, two complementary articles highlight the neural mechanisms underlying the localization of an odor, either to the left or right side of the nose (Porter et al.) or to the inside or outside of the mouth (Small et al.). Together, these studies validate the idea that the human brain is equipped with the apparatus necessary to pinpoint the location of an odor source.

Differential neural responses evoked by orthonasal versus retronasal odorant perception in humans.

Odors perceived through the mouth (retronasally) as flavor are referred to the oral cavity, whereas odors perceived through the nose (orthonasally) are referred to the external world. We delivered vaporized odorants via the orthonasal and retronasal routes and measured brain response with fMRI. Comparison of retronasal versus orthonasal delivery produced preferential activity in the mouth area at the base of the central sulcus, possibly reflecting olfactory referral to the mouth, associated with retronasal olfaction. Routes of delivery produced differential activation in the insula/operculum, thalamus, hippocampus, amygdala, and caudolateral orbitofrontal cortex in orthonasal > retronasal and in the perigenual cingulate and medial orbitofrontal cortex in retronasal > orthonasal in response to chocolate, but not lavender, butanol, or farnesol, so that an interaction of route and odorant may be inferred. These findings demonstrate differential neural recruitment depending upon the route of odorant administration and suggest that its effect is influenced by whether an odorant represents a food.

Investigations on multimodal sensory integration: texture, taste, and ortho- and retronasal olfactory stimuli in concert.

Perceptual interactions between odour and oral texture were explored in a study in which a cream odour was presented ortho- or retronasally at well-defined moments whilst milk-like foods with different viscosities, produced by adding a thickener, were present in the mouth. Gaseous (odour) and liquid (texture) pulses were presented using a specially-developed computer-controlled system of air-dilution olfactometry and pumps. Odour pulses, lasting 2 s, were presented either during a 3-s period in which a liquid filled the oral cavity, during a 3-s period in which the liquid was manipulated orally or during the swallowing of the liquid. Subjects rated the intensity of overall flavour, thickness and creaminess. Perceived flavour intensity was reduced with increasing viscosity of the liquid, irrespective of whether or not the odour was presented ortho- or retronasally. The odour stimulus increased the intensities of thickness and creaminess, but only when the odour was presented retronasally that is as if the odour would have originated from the liquid. Furthermore, this enhancement was most pronounced when odours coincided with swallowing, less pronounced when odours coincided with oral manipulation and absent when presented during mouth filling. The results suggest that cross-modal interactions are the rule rather than the exception, provided that multi-modal sensory integration has occurred.

Taste, olfactory, and food texture processing in the brain, and the control of food intake.

Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature, and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. In the orbitofrontal cortex, feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour, and the activation produced by the odour in the orbitofrontal cortex. These findings provide a basis for understanding how what is in the mouth is represented by independent information channels in the brain; how the information from these channels is combined; and how and where the reward and subjective affective value of food is represented and is influenced by satiety signals. Activation of these representations in the orbitofrontal cortex may provide the goal for eating, and understanding them helps to provide a basis for understanding appetite and its disorders.

Re-examining jaw regeneration in urodeles: what have we learnt?

Urodele amphibians can regenerate not only their limbs and tails, but also their upper and lower jaws rather faithfully. However, relatively few studies of jaw regeneration in amphibians have been carried out, especially in recent years. It is therefore important to reexamine thoroughly this regenerating system, since the advent of sophisticated morphological techniques and the development of molecular approaches offer the promise of renewed and rapid progress in our understanding of complex developmental problems such as this. This paper briefly reviews some of the early research on jaw regeneration, some of the fundamental questions which have been asked and have yet to be answered, and the work we have carried out in order to understand the molecular mechanisms underlying jaw regeneration in the newt, Notophthalmus viridescens. In addition, some aspects of jaw regeneration will be discussed in relation to regeneration of the adult limb.

FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects.

Olfactory function is affected by aging and deficits often result in decreasing quality of life, health and safety. The present study investigated the cortical substrate of olfactory deficits related to aging with functional Magnetic Resonance Imaging (fMRI), with a retronasal olfactory stimulation protocol using flavored aqueous solutions presented to the mouth. Activation was found in young subjects in the piriform/amygdalar region and in the orbitofrontal cortex and in other areas previously found activated in neuroimaging studies using odorized air, including insula and cerebellum. Activation was seen in similar areas in old subjects but the degree of activation was significantly lower in regions receiving primary olfactory projections (piriform cortex, entorhinal cortex, and amygdala). This result supports the hypothesis of dysfunction and/or degeneration in areas critical to olfactory processing as a major cause of olfactory deficits in the older population.

[Chromatographic fractionation of scraping components of frog olfactory tissues. Preparation of fractions capable of sensitizing artificial lipid membrane to odorants]. / Khromatograficheskoe razdelenve komponentov soskoba oboniatel'noi vystilki liagushki. Poluchenie fraktsii, sposobnykh sensibilizirouat' isku sstvennye fosfolipidnye membrany k deistviiu pakhuchikh veshchestv.

The fractionation of frog olfactory preparation by ion-exchange chromatography and gel filtration permitted to obtain fractions capable of making artificial lipid membranes sensitive to odorants, such as camphora, musc ambrette and linalool. The sensitizing agent present in active fractions is a high-molecular-weight (m.w. 100,000) protein containing substance. It is suggested that this agent is a component of a special transport system which may carry the odorous molecules to olfactory receptor cells or to remove them from olfactory tissues.

Temporal processing of olfactory stimuli during retronasal perception.

Odorants can be perceived via the nose during an inhalation or sniff (orthonasal perception) and via the mouth, nasopharynx and nasal cavity during mastication or drinking (retronasal perception). Previous data suggest that orthonasal perception provides a more efficient route with greater difficulty being reported when detecting [Halpern BP. Retronasal and orthonasal smelling. Chemosense 2004;6:1-7; Voirol E, Daget N. Comparative study of nasal and retronasal olfactory perception. Lebensmittel-Wissenschaft Technol 1986;19:316-9] and identifying [Heilmann S, Hummel T. A new method for comparing orthonasal and retronasal olfaction. Behav Neurosci 2004;118:412-9; Sun BC, Halpern BP. Identification of air-phase retronasal and orthonasal odorant pairs. Chem Senses 2005;30:1-14] single odorants retronasally. Whether the poorer sensitivity obtained via the retronasal route is largely due to the greater adsorption of odorants by the nasopharyngeal mucus compared to the nasal mucus thereby reducing their peak concentration and/or slowing their passage, has not been resolved. Importantly, the question of whether solubility of odorants in mucus or water predicts the outcomes for perception of stimuli presented via the retronasal route has not been resolved. Accordingly, the present study investigates this question by determining whether the solubility of an odorant in mucus predicts which component of a binary odour mixture is perceived first during retronasal perception. The results indicate that solubility in mucus rather than solubility in water is a better predictor of which odour will be perceived first and identified more readily during the retronasal perception of a binary mixture. In addition, lower intensity levels of single odorants occurred via the retronasal route suggesting that adsorption was greater via this route. Whether this was due to nasopharyngeal mucus having a greater adsorptive area or different composition compared to the orthonasal pathway is not known.

An experimental biomimetic platform for artificial olfaction.

Artificial olfactory systems have been studied for the last two decades mainly from the point of view of the features of olfactory neuron receptor fields. Other fundamental olfaction properties have only been episodically considered in artificial systems. As a result, current artificial olfactory systems are mostly intended as instruments and are of poor benefit for biologists who may need tools to model and test olfactory models. Herewith, we show how a simple experimental approach can be used to account for several phenomena observed in olfaction. An artificial epithelium is formed as a disordered distributed layer of broadly selective color indicators dispersed in a transparent polymer layer. The whole epithelium is probed with colored light, imaged with a digital camera and the olfactory response upon exposure to an odor is the change of the multispectral image. The pixels are treated as olfactory receptor neurons, whose optical properties are used to build a convergence classifier into a number of mathematically defined artificial glomeruli. A non-homogenous exposure of the test structure to the odours gives rise to a time and spatial dependence of the response of the different glomeruli strikingly similar to patterns observed in the olfactory bulb. The model seems to mimic both the formation of glomeruli, the zonal nature of olfactory epithelium, and the spatio-temporal signal patterns at the glomeruli level. This platform is able to provide a readily available test vehicle for chemists developing optical indicators for chemical sensing purposes and for biologists to test models of olfactory system organization.

Sensory processing in the brain related to the control of food intake.

Complementary neurophysiological recordings in rhesus macaques (Macaca mulatta) and functional neuroimaging in human subjects show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. In the orbitofrontal cortex feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including the human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour, and the activation produced by the odour in the orbitofrontal cortex. Food intake is thus controlled by building a multimodal representation of the sensory properties of food in the orbitofrontal cortex and gating this representation by satiety signals to produce a representation of the pleasantness or reward value of food that drives food intake. Factors that lead this system to become unbalanced and contribute to overeating and obesity are described.

Innervation pattern of suboesophageal ventral unpaired median neurones in the honeybee brain.

In honeybees (Apis mellifera), the biogenic amine octopamine has been shown to play a role in associative and non-associative learning and in the division of labour in the hive. Immunohistochemical studies indicate that the ventral unpaired median (VUM) neurones in the suboesophageal ganglion (SOG) are putatively octopaminergic and therefore might be involved in the octopaminergic modulation of behaviour. In contrast to our knowledge about the behavioural effects of octopamine, only one neurone (VUMmx1) has been related to a behavioural effect (the reward function during olfactory learning). In this study, we have investigated suboesophageal VUM neurones with fluorescent dye-tracing techniques and intracellular recordings combined with intracellular staining. Ten different VUM neurones have been found including six VUM neurones innervating neuropile regions of the brain and the SOG exclusively (central VUM neurones) and four VUM neurones with axons in peripheral nerves (peripheral VUM neurones). The central VUM neurones innervate the antennal lobes, the protocerebral lobes (including the lateral horn) and the mushroom body calyces. Of these, a novel mandibular VUM neurone, VUMmd1, exhibits the same branching pattern in the brain as VUMmx1 and responds to sucrose and odours in a similar way. The peripheral VUM neurones innervate the antennal and the mandibular nerves. In addition, we describe one labial unpaired median neurone with a dorsal cell body, DUMlb1. The possible homology between the honeybee VUM neurones and the unpaired median neurones in other insects is discussed.

Olfactory responses in a gustatory organ of the malaria vector mosquito Anopheles gambiae.

The proboscis is an important head appendage in insects that has primarily been thought to process gustatory information during food intake. Indeed, in Drosophila and other insects in which they have been identified, most gustatory receptors are expressed in proboscis neurons. Our previous characterization of the expression of AgOR7, a highly conserved odorant receptor (OR) of the Afrotropical malaria vector mosquito Anopheles gambiae in the labellum at the tip of the proboscis was suggestive of a potential olfactory function in this mosquito appendage. To test this hypothesis, we used electrophysiological recording and neuronal tracing, and carried out a molecular characterization of candidate OR expression in the labellum of A. gambiae. These studies have uncovered a set of labial olfactory responses to a small spectrum of human-related odorants, such as isovaleric acid, butylamine, and several ketones and oxocarboxylic acids. Molecular analyses indicated that at least 24 conventional OR genes are expressed throughout the proboscis. Furthermore, to more fully examine AgOR expression within this tissue, we characterized the AgOR profile within a single labial olfactory sensillum. This study provides compelling data to support the hypothesis that a cryptic set of olfactory neurons that respond to a small set of odorants are present in the mouth parts of hematophagous mosquitoes. This result is consistent with an important role for the labellum in the close-range discrimination of bloodmeal hosts that directly impacts the ability of A. gambiae to transmit malaria and other diseases.

Neuronal representations of stimuli in the mouth: the primate insular taste cortex, orbitofrontal cortex and amygdala.

The responses of 3687 neurons in the macaque primary taste cortex in the insula/frontal operculum, orbitofrontal cortex (OFC) and amygdala to oral sensory stimuli reveals principles of representation in these areas. Information about the taste, texture of what is in the mouth (viscosity, fat texture and grittiness, which reflect somatosensory inputs), temperature and capsaicin is represented in all three areas. In the primary taste cortex, taste and viscosity are more likely to activate different neurons, with more convergence onto single neurons particularly in the OFC and amygdala. The different responses of different OFC neurons to different combinations of these oral sensory stimuli potentially provides a basis for different behavioral responses. Consistently, the mean correlations between the representations of the different stimuli provided by the population of OFC neurons were lower (0.71) than for the insula (0.81) and amygdala (0.89). Further, the encoding was more sparse in the OFC (0.67) than in the insula (0.74) and amygdala (0.79). The insular neurons did not respond to olfactory and visual stimuli, with convergence occurring in the OFC and amygdala. Human psychophysics showed that the sensory spaces revealed by multidimensional scaling were similar to those provided by the neurons.

Is feeding behaviour in crucian carp mediated by the lateral olfactory tract?

Experiments were performed to investigate which bundle of the olfactory tract was essential for mediating feeding behaviour in crucian carp. Fish were divided in three groups: control fish, fish with only the lateral olfactory tracts (LOTs) intact and fish with the LOTs cut. The fish were maintained in physiological saline after surgery to preserve the remaining tracts and postoperative inspections revealed the functional status of the remaining tracts. With the injection of food odour into the aquaria the scores for various feeding behaviours--biting, snapping, mouth openings and vertical posture--were not significantly different between those of the control fish and the fish with the LOT intact. Those fish that had the LOT cut but the medial and lateral parts of the medial olfactory tract (mMOT, lMOT) intact had significantly lower feeding-related scores than the other two groups of fish. The results of the present study indicate that the LOT is necessary to maintain the full qualitative and quantitative extent of feeding behaviour in crucian carp.

Breathing and upper airway CO2 in reptiles: role of the nasal and vomeronasal systems.

The ventilatory response of the garter snake, Thamnophis sirtalis, to 2% CO2 delivered to the upper airways (UA) was measured before and after the olfactory or vomeronasal nerves were transected. The UA (nasal cavities and mouth) were isolated from the gas source inspired into the lungs by inserting an endotracheal T tube into the glottis. CO2 was administered to the UA via a head chamber. The primary ventilatory response to UA CO2 was a significant decrease in ventilatory frequency (f) and minute ventilation. The decrease in f was caused by a significant increase in the pause duration. Tidal volume, expiratory duration, and inspiratory duration were not altered with UA CO2. The f response to UA CO2 was abolished with olfactory nerve transection, whereas vomeronasal nerve transection significantly increased the magnitude of the f depression. These results indicate that CO2-sensitive receptors are located in the nasal epithelium and that the olfactory nerves must be intact for the UA CO2 f response to be observed. In addition, the vomeronasal system appears to modulate the ventilatory response to UA CO2.

Integrative properties of the Pe1 neuron, a unique mushroom body output neuron.

A mushroom body extrinsic neuron, the Pe1 neuron, connects the peduncle of the mushroom body (MB) with two areas of the protocerebrum in the honeybee brain, the lateral protocerebral lobe (LPL) and the ring neuropil around the alpha-lobe. Each side of the bee brain contains only one Pe1 neuron. Using a combination of intracellular recording and neuroanatomical techniques we analyzed its properties of integrative processing of the different sensory modalities. The Pe1 neuron responds to visual, mechanosensory, and olfactory stimuli. The responses are broadly tuned, consisting of a sustained increase of spike frequency to the onset and offset of light flashes, to horizontal and vertical movements of extended objects, to mechanical stimuli applied to the antennae or mouth parts, and to all olfactory stimuli tested (29 chemicals). These multisensory properties are reflected in its dendritic organization. Serial reconstructions of intracellularly stained Pe1 neurons using confocal microscopy reveal that the Pe1 neuron arborizes throughout all layers of MB peduncle with finger-like, vertically oriented dendrites. The peduncle of the MB is formed by the axons of Kenyon cells, whose dendritic inputs are organized in modality-specific subcompartments of the calyx region. The peduncular arborization indicates that the Pe1 neuron receives input from Kenyon cells of all calycal subcompartments. Because the Pe1 neuron changes its odor responses transiently as a consequence of olfactory learning, we hypothesize that the multimodal response properties might have a role in memory consolidation and help to establish contextual references in the long-term trace.