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Organization of receptive surfaces reflects primary axes of perception. In vision, retinal coordinates reflect spatial coordinates. In audition, cochlear coordinates reflect tonal coordinates. However, the rules underlying the organization of the olfactory receptive surface are unknown. To test the hypothesis that organization of the olfactory epithelium reflects olfactory perception, we inserted an electrode into the human olfactory epithelium to directly measure odorant-induced evoked responses. We found that pairwise differences in odorant pleasantness predicted pairwise differences in response magnitude; that is, a location that responded maximally to a pleasant odorant was likely to respond strongly to other pleasant odorants, and a location that responded maximally to an unpleasant odorant was likely to respond strongly to other unpleasant odorants. Moreover, the extent of an individual's perceptual span predicted their span in evoked response. This suggests that, similarly to receptor surfaces for vision and audition, organization of the olfactory receptor surface reflects key axes of perception.

author can archive publisher's version/PDF (embargo 6 months) ; 1529-2401 (Electronic ISSN); International audience; To sense myriad environmental odors, animals have evolved multiple, large families of divergent olfactory receptors. How and why distinct receptor repertoires and their associated circuits are functionally and anatomically integrated is essentially unknown. We have addressed these questions through comprehensive comparative analysis of the Drosophila olfactory subsystems that express the ionotropic receptors (IRs) and odorant receptors (ORs). We identify ligands for most IR neuron classes, revealing their specificity for select amines and acids, which complements the broader tuning of ORs for esters and alcohols. IR and OR sensory neurons exhibit glomerular convergence in segregated, although interconnected, zones of the primary olfactory center, but these circuits are extensively interdigitated in higher brain regions. Consistently, behavioral responses to odors arise from an interplay between IR- and OR-dependent pathways. We integrate knowledge on the different phylogenetic and developmental properties of these receptors and circuits to propose models for the functional contributions and evolution of these distinct olfactory subsystems.

SummaryElectrophysiological investigations in locusts have revealed that the sparseness of odor representations, in the brain region expected to mediate olfactory learning, is shaped by a unique inhibitory neuron.

Following the discovery of olfactory receptors (ORs) in 1999 (Clyne et al., 1999; Vosshall et al., 1999), our understanding of the first steps in olfactory coding in Drosophila melanogaster has grown exponentially. The expression of ORs follows the general rule of one OR to one olfactory sensory neuron (OSN). Characterization of ORs, OSNs, and their locations in different sensilla at OR organs (i.e., antennae and maxillary palps) has been completed (Hallem and Carlson, 2004; Vosshall and Stocker, 2007). Moreover, the map of neuronal connections made into specific glomeruli of the antennal lobe has also been reported (Fishilevich and Vosshall, 2005). This structural description of olfactory sensory elements has been followed by the functional characterization of the olfactory profiles of different ORs expressed in the so-called “empty neuron” system (Hallem and Carlson, 2006) as well as in their native OSNs (de Bruyne et al., 2001; Hallem et al., 2004). Particular attention has been paid to the transduction process that converts the odor signal into a pattern of spikes in the OSNs. It was found that the ligand-binding ORs and their common OR83b coreceptor (now renamed Orco; Vosshall and Hansson, 2011), which form a heterodimer, exhibit an inverted topology compared to other G protein coupled receptors (Benton et al., 2006; Lundin et al., 2007). In 2008, two papers published in Nature reported the use of heterologous systems transfected with Orco and one of the ORs to show that this heterodimer can act in an ionotropic manner (Sato et al., 2008; Wicher et al., 2008). However, one of these papers also reported an additional metabotropic component that was dependent on G proteins (Wicher et al., 2008). Another article using the same techniques also supported the ionotropic model (Smart et al., 2008). Reports using genetically modified flies with mutated G proteins either supported (Kain et al., 2008; Chatterjee et al., 2009; Deng et al., 2011) or argued against (Yao and Carlson, 2010) the metabotropic component in the function of the OR–Orco heterodimer. Two hypotheses have been proposed to explain these results. It is possible that the insect ORs may be mixed ionotropic–metabotropic receptors (Wicher, 2010), or alternatively, insect ORs may be metabotropically modulated ionotropic receptors (Nakagawa and Vosshall, 2009). In the article published in Frontiers of Cellular Neuroscience vol. 5, June 2011, the group of Wicher and Hansson present new and interesting data that further our understanding of how the OR + Orco heterodimer functions by studying the regulation of one of its components, the Orco channel (Wicher et al., 2009). In this report, the authors show that the Orco channel activity is regulated by phosphorylation via protein kinase C (PKC), which is activated by the phospholipase C (PLC) intermediate in the inositol 1,4,5-triphosphate/diacyl glycerol (IP3/DAG) transduction cascade. Wicher and Hansson employ a multidisciplinary approach, including the use of cells in culture transfected with the Orco gene to study the channel's sensitivity to cyclic adenosine monophosphate (cAMP) in the presence of different activators and inhibitors. These experiments show that G proteins do not activate the Orco channel and that DAG, but not IP3, directly affects the activity of this channel. Similar results concerning the importance of DAG as second messenger have been described in the visual transduction system of insects (Hardie et al., 2002). However, a more indirect role for IP3 in olfactory transduction cannot be excluded because changes in the expression of IP3kinase1 in OSNs have been reported to affect olfactory perception (Gomez-Diaz et al., 2006). In this case, the authors show evidence that PKC, which is activated by DAG, controls the function of the Orco channel. To confirm the action of PKC, the authors tested three mutant versions of the Orco gene that were modified in different PKC phosphorylation sites. Finally, in an attempt to understand the in vivo situation, single sensilla recordings were performed in normal flies in response to odorants after the injection of excitatory or inhibitory agents for PLC and PKC. The findings were compatible with the observations obtained from cell culture experiments. The authors point out that they are not seeking to determine in the article whether insect ORs are mixed ionotropic and metabotropic receptors (Wicher, 2010) or metabotropically modulated ionotropic receptors (Nakagawa and Vosshall, 2009); however, these results could represent a step toward addressing this question. The use of the Orco mutant clones generated in this work, when combined with ORs in heterologous systems or expressed in flies for in vivo studies, could serve as helpful tools in future investigations. Nevertheless, even if the binding of odorant molecules to the OR–Orco dimers does not directly activate a metabotropic cascade, the results reported in this article confirm an important role for a metabotropic component in olfactory reception. The single sensilla recordings, performed after microinjection of various pharmacological agents, demonstrated that OSNs can be metabotropically affected by modulating phosphorylation, which is in agreement with the results obtained using transfected cells. In insects, it has been reported that a single OSN can have excitatory and inhibitory responses to different odorants (Hallem and Carlson, 2006), but the mechanisms that explain this phenomenon are not known. The observed up- and downregulation of PLC/PKC may account, at least in part, for such differences if odor binding modulates the level of PKC in OSNs. Finally, according to these results, the Orco channel is regulated by the interaction of elements of the IP3/DAG and cAMP transduction cascades. The existence of such a crosstalk between transduction cascades has been previously suggested in the vertebrate olfactory transduction system related to PLC, cAMP, and a kinase, in this case protein kinase A, although the mechanism of action and the ionic channel involved was not described (Vogl et al., 2000). The new findings regarding crosstalk between both transduction cascades and the Orco channel could also shed light on the mechanisms of regulation by metabotropic cascades in other systems and organisms.

Most natural odors are mixtures and often elicit percepts distinct from those elicited by their constituents. This emergence of a unique odor quality has long been attributed to central processing. Here we show that sophisticated integration of olfactory information begins in olfactory receptor neurons (ORNs) in Drosophila . Odor mixtures are encoded in the temporal dynamics as well as in the magnitudes of ORN responses. ORNs can respond to an inhibitory odorant with different durations depending on the level of background excitation. ORNs respond to mixtures with distinctive temporal dynamics that reflect the physicochemical properties of the constituent odorants. The insect repellent DEET ( N , N -diethyl- m -toluamide), which attenuates odor responses of multiple ORNs, differs from an ORN-specific inhibitor in its effects on temporal dynamics. Our analysis reveals a means by which integration of information from odor mixtures begins in ORNs and provides insight into the contribution of inhibitory stimuli to sensory coding.

The olfactory system excels in both discrimination and detection of odorants. In mammals, it reliably discriminates more than 3000 structurally diverse odorant molecules and has an amazingly high sensitivity that allows the detection of very low amounts of specific odorant molecules. In addition, the olfactory system has the capability to adapt to ambient odorants, allowing the recognition of a broad range of stimuli. The discrimination among different odorants is achieved by using hundreds of receptors, activated with a combinatorial code. Olfactory transduction uses a canonical second messenger system providing two critical attributes: amplification and high signal-to-noise characteristics, giving the system its remarkable detector capabilities. In this review, we present an introduction to the basic molecular mechanisms of olfactory transduction in olfactory sensory neurons.

Insects have gustatory receptors with which they taste chemicals and make important choices about foods, mates, and egg deposition sites. Gustatory receptors are novel proteins, and understanding how they recognize diverse chemicals is an unmet challenge. We developed a method to examine taste receptor function using a Drosophila olfactory neuron as a host for expressing taste receptors. We individually tested all sweet receptors of the fly, which resulted in specific sugar responses in the olfactory neuron. We also successfully expressed a bitter receptor and a mosquito taste receptor. Our study describes a systematic view of how the fly’s taste receptors detect sweet substances and holds promise for uncovering functions of taste receptors from insects that transmit diseases or damage crops.

The olfactory system detects and discriminates myriad chemical structures across a wide range of concentrations. To meet this task, the system utilizes a large family of G protein–coupled receptors—the odorant receptors—which are the chemical sensors underlying the perception of smell. Interestingly, the odorant receptors are also involved in a number of developmental decisions, including the regulation of their own expression and the patterning of the olfactory sensory neurons' synaptic connections in the brain. This review will focus on the diverse roles of the odorant receptor in the function and development of the olfactory system.

The generation of new cells in the adult brain reveals a new form of plasticity in the neuronal network. New cells are constantly migrating to and integrating into the pre-existing neuronal network in the olfactory bulb. The exact role of new neurons in the adult olfactory bulb and in odor behavior remains elusive despite continuous progress. The unique properties of these adult-born interneurons that distinguish them from pre-existing bulbar neurons allow them to adapt the processing of odor information in the neuronal network of the olfactory bulb in response to sensory experience. The combination of diverse methods for modulating neurogenesis levels with distinct behavioral paradigms has revealed that interneurons generated during adulthood play a role in olfactory behavior. In this review we provide an overview of the unique properties of adult-born neurons that integrate into the olfactory bulb as well as their role in odor behavior.

The response of insect olfactory receptor neurons (ORNs) to odorants involves the opening of Ca2+-permeable channels, generating an increase in intracellular Ca2+concentration. Here, we studied the downstream effect of this Ca2+rise in cultured ORNs of the mothSpodoptera littoralis. Intracellular dialysis of Ca2+from the patch pipette in whole-cell patch-clamp configuration activated a conductance with aK1/2of 2.8 μm. Intracellular and extracellular anionic and cationic substitutions demonstrated that Cl−carries this current. The anion permeability sequence I−> NO3−> Br−> Cl−> CH3SO3−≫ gluconate−of the Ca2+-activated Cl−channel suggests a weak electrical field pore of the channel. The Ca2+-activated current partly inactivated over time and did not depend on protein kinase C (PKC) and CaMKII activity or on calmodulin. Application of Cl−channel blockers, flufenamic acid, 5-nitro-2-(3-phenylpropylamino) benzoic acid, or niflumic acid reversibly blocked the Ca2+-activated current. In addition, lowering Cl−concentration in the sensillar lymph bathing the ORN outer dendrites caused a significant delay in pheromone response terminationin vivo. The present work identifies a new Cl−conductance activated by Ca2+in insect ORNs presumably required for ORN repolarization.

Mammalian olfactory system is the archetype of smell sensor devices. Its complexity resides both in the odorant mechanism of capture by the single olfactory receptor (OR) and in the space organization and codification of the information. The result is a unique profile for each odorant. Our aim is to partially mimick this system, in order to produce a biosensor on nanometric scale. In this paper, we present a microscopic theoretical framework in which the experimental results should be embedded. It consists of the description of the protein at the level of the amino-acid structure in terms of an impedance network able to simulate the electrical characteristics associated with the protein topology.

International audience; The molecular mechanisms that control the binding of odorant to olfactory receptors and transduce this signal into membrane depolarization are reviewed. They are compared in vertebrates and insects for interspecific (allelochemicals) and intraspecific (pheromones) olfactory signals. Attempts to develop quantitative models of these multistage signalling networks are presented. Computational analysis of olfactory transduction is still in its infancy and appears as a promising area for future developments.

Complex sensory systems such as the olfactory transduction pathway considered in this paper are known to exhibit two distinct types of adaptation: long term adaptation in response to step-like stimulations and short-term adaptation in response to sequences of pulse-like stimuli. We show in this paper that perfect adaptation models such as the integral feedback scheme are unable to explain both these phenomena simultaneously, but that a leaky integral feedback (i.e., a dynamical compensator including also a slow degradation term) reproduces well all experimental data available.

We measured frequency response functions between concentrations of fruit odorants and individual action potentials in large basiconic sensilla of the Drosophila melanogaster antenna. A new method of randomly varying odorant concentration was combined with rapid, continuous measurement of concentration at the antenna by a miniature photoionization detector. All frequency responses decreased progressively at frequencies approaching 100 Hz, providing an upper limit for the dynamics of Drosophila olfaction. We found two distinct response patterns: excitatory band-pass frequency responses were seen with ethyl acetate, ethyl butyrate, and hexanol, whereas inhibitory low-pass responses were seen with methyl salicylate and phenylethyl acetate. Band-pass responses peaked at 1–10 Hz. Frequency responses could be well fitted by simple linear filter equations, and the fitted parameters were consistent within each of the two types of responses. Experiments with equal mixtures of excitatory and inhibitory odorants gave responses that were characteristic of the inhibitory components, indicating that interaction during transduction causes inhibitory odorants to suppress the responses to excitatory odorants. Plots of response amplitude versus odorant concentration indicated that the odorant concentrations used were within approximately linear regions of the dose response relationships. We also estimated linear information capacity from the coherence function of each recording. Although coherence was relatively high, indicating a large signal-to-noise ratio, information capacity for olfaction was much lower than comparable estimates for mechanotransduction or visual transduction because of the limited bandwidth of olfaction. These data offer new insights into transduction by primary chemoreceptors and place temporal constraints on Drosophila olfactory behavior.

A biophysical model of receptor potential generation in the male moth olfactory receptor neuron is presented. It takes into account all pre-effector processes—the translocation of pheromone molecules from air to sensillum lymph, their deactivation and interaction with the receptors, and the G-protein and effector enzyme activation—and focuses on the main post-effector processes. These processes involve the production and degradation of second messengers (IP3 and DAG), the opening and closing of a series of ionic channels (IP3-gated Ca2+ channel, DAG-gated cationic channel, Ca2+-gated Cl− channel, and Ca2+- and voltage-gated K+ channel), and Ca2+ extrusion mechanisms. The whole network is regulated by modulators (protein kinase C and Ca2+-calmodulin) that exert feedback inhibition on the effector and channels. The evolution in time of these linked chemical species and currents and the resulting membrane potentials in response to single pulse stimulation of various intensities were simulated. The unknown parameter values were fitted by comparison to the amplitude and temporal characteristics (rising and falling times) of the experimentally measured receptor potential at various pheromone doses. The model obtained captures the main features of the dose–response curves: the wide dynamic range of six decades with the same amplitudes as the experimental data, the short rising time, and the long falling time. It also reproduces the second messenger kinetics. It suggests that the two main types of depolarizing ionic channels play different roles at low and high pheromone concentrations; the DAG-gated cationic channel plays the major role for depolarization at low concentrations, and the Ca2+-gated Cl− channel plays the major role for depolarization at middle and high concentrations. Several testable predictions are proposed, and future developments are discussed., Author Summary All sensory neurons transduce their natural stimulus, whether a molecule, a photon, or a mechanical force, in an electrical current flowing through their sensory membrane via similar molecular and ionic mechanisms. Olfactory receptor neurons (ORNs), whose stimuli are volatile molecules, are no exception, including one of the best known: the exquisitely sensitive ORNs of male moths that detect the sexual pheromone released by conspecific females. We provide a detailed computational model of the intracellular molecular mechanisms at work in this ORN type. We describe qualitatively and quantitatively how the initial event, the interaction of pheromone molecules with specialized receptors at the ORN surface, is amplified through a sequence of linked biochemical and electrical events into a whole cell response, the receptor potential. We detail the respective roles of the upward activating reactions involving a cascade of ionic channels permeable to cations, chloride and potassium, their control by feedback inactivating mechanisms, and the central regulatory role of calcium. This computational model contributes to an integrated understanding of this signalling pathway, provides testable hypotheses, and suggests new experimental approaches.

Many vertebrates possess at least two distinct olfactory systems, a main olfactory and an accessory olfactory system, both of which are capable of detecting and transducing molecular cues of social nature, such as pheromones. This article summarizes basic features of the physiology and function of the accessory olfactory system, which includes the vomeronasal organ and the accessory olfactory bulb.

Individual glomeruli in the vertebrate olfactory bulb represent a single odorant receptor. The glomerular sheet of the olfactory bulb thus forms odorant receptor maps. Using a variety of methods, recent mapping studies show that (1) individual glomeruli respond to a range of odorants that share a specific combination of molecular features, (2) each glomerulus appears to be unique in its odorant molecular feature specificity, and (3) glomeruli with similar molecular feature specificity gather together in proximity and form molecular feature clusters. Odorant molecular features are thus represented systematically and multidimensionally in the glomerular maps of the olfactory bulb.

Recent studies of the projection pattern made by sensory neurons involved in mammalian pheromone reception have shown that there is a map of activation in the brain, but this pheromone map appears far more complex than the equivalent map in the main olfactory system responsible for the sense of smell.

Publisher Summary Cyclic nucleotides exert their physiological effects by binding to four major classes of cellular receptors: cAMP- and cGMP-dependent protein kinases, cyclic GMP-regulated phosphodiesterases, cAMP-binding guanine nucleotide exchange factors, and cyclic nucleotide-regulated cation channels. Two families of channels regulated by cyclic nucleotides are: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. CNG and HCN channels are members of the superfamily of voltage-gated cation channels. The two channel classes differ from each other with regard to their mode of activation. CNG channels are opened by direct binding of cAMP or cGMP. In contrast, HCN channels are principally operated by voltage. These channels open at hyperpolarized membrane potentials, and close on depolarization. HCN channels are also activated directly by cyclic nucleotides, which act by increasing the channel open probability. CNG channels are expressed in retinal photoreceptors and olfactory neurons, and play a key role in visual and olfactory signal transduction. CNG channels are also found at low density in some other cell types and tissues, such as brain, testis, and kidney. A cation current that is slowly activated by membrane hyperpolarization (termed Ih, If, or Iq) is found in a variety of excitable cells, including neurons, cardiac pacemaker cells, and photoreceptors. The best established function of Ih is to control heart rate and rhythm by acting as “pacemaker current” in the sinoatrial (SA) node.

The computational role of the olfactory bulb remains a mystery after 60 yr of physiological research. Recently, Fantana and colleagues proposed a new model of bulb function based on sparse inhibitory connections between glomeruli, the functional units of the bulb, rather than the existing lateral inhibition model. I present a summary of their model here and its implications along with comparison to recent work in the very similar Drosophila olfactory system.

In addition to the main olfactory system, many vertebrates have developed an accessory olfactory system (AOS). The AOS consists of the vomeronasal organ (VNO), a chemoreceptive structure situated at the base of the nasal septum which houses the vomeronasal sensory neurons; the accessory olfactory bulb (AOB), a structure of the forebrain that receives input from the VNO serving as the first processing center of vomeronasal information; and higher olfactory centers that receive direct or indirect information from the AOB. This chapter provides a general overview about the physiology and function of the VNO and AOB.

Molecular approaches and genetic manipulations have provided novel insights into the processing of pheromone-mediated information by the olfactory and vomeronasal systems of mammals. We will review and discuss the specific contribution of each of the two chemosensory systems that ensure specific behavioral responses to conspecific animals.

Odor transduction and quality coding involves a cascade of events that occur at the level of the olfactory epithelium and olfactory bulbs. Odorants bind to one or a few specific olfactory receptors

Components of odor mixtures often are not perceived individually, suggesting that neural representations of mixtures are not simple combinations of the representations of the components. We studied odor responses to binary mixtures of amino acids and food extracts at different processing stages in the olfactory bulb (OB) of zebrafish. Odor-evoked input to the OB was measured by imaging Ca2+signals in afferents to olfactory glomeruli. Activity patterns evoked by mixtures were predictable within narrow limits from the component patterns, indicating that mixture interactions in the peripheral olfactory system are weak. OB output neurons, the mitral cells (MCs), were recorded extra- and intracellularly and responded to odors with stimulus-dependent temporal firing rate modulations. Responses to mixtures of amino acids often were dominated by one of the component responses. Responses to mixtures of food extracts, in contrast, were more distinct from both component responses. These results show that mixture interactions can result from processing in the OB. Moreover, our data indicate that mixture interactions in the OB become more pronounced with increasing overlap of input activity patterns evoked by the components. Emerging from these results are rules of mixture interactions that may explain behavioral data and provide a basis for understanding the processing of natural odor stimuli in the OB.

Vomeronasal sensory neurons play a crucial role in detecting pheromones, but the chemoelectrical transduction mechanism remains unclear and controversial. A major barrier to the resolution of this question has been the lack of an activation mechanism of a key transduction component, the TRPC2 channel. We have identified a Ca 2+ -permeable cation channel in vomeronasal neuron dendrites that is gated by the lipid messenger diacylglycerol (DAG), independently of Ca 2+ or protein kinase C. We demonstrate that ablation of the TRPC2 gene causes a severe deficit in the DAG-gated channel, indicating that TRPC2 encodes a principal subunit of this channel and that the primary electrical response to pheromones depends on DAG but not Ins(1,4,5)P 3 , Ca 2+ stores, or arachidonic acid. Thus, a previously unanticipated mechanism involving direct channel opening by DAG underlies the transduction of sensory cues in the accessory olfactory system.

The exquisite specificity in the organization of the mammalian olfactory system underlies its remarkable sensitivity and precision in odorant detection. The contribution of olfactory receptor proteins to the initial patterning of connections between the sensory epithelium and the bulb is widely appreciated. The application of genetic model systems has revealed additional roles for odorant-evoked activity in the development, organization and dynamic turnover of cells in this regenerating sensory organ.

Odor perception depends on a constellation of molecular, cellular, and network interactions in olfactory brain areas. Recently, there has been better understanding of the cellular and molecular mechanisms underlying the odor responses of neurons in the olfactory epithelium, the first-order olfactory area. In higher order sensory areas, synchronized activity in networks of neurons is known to be a prominent feature of odor processing. The perception and discrimination of odorants is associated with fast (20–70 Hz) electroencephalographic oscillations. The cellular mechanisms underlying these fast network oscillations have not been defined. In this study, we show that synchronous fast oscillations can be evoked by brief electrical stimulation in the rat olfactory bulb in vitro, partially mimicking the natural response of this brain region to sensory input. Stimulation induces periodic inhibitory synaptic potentials in mitral cells and prolonged spiking in GABAergic granule cells. Repeated stimulation leads to the persistent enhancement in both granule cell activity and mitral cell inhibition. Prominent oscillations in field recordings indicate that stimulation induces high-frequency activity throughout networks of olfactory bulb neurons. Network synchronization results from chemical and electrical synaptic interactions since both glutamate-receptor antagonists and gap junction inhibitors block oscillatory intracellular and field responses. Our results demonstrate that the olfactory bulb can generate fast oscillations autonomously through the persistent activation of networks of inhibitory interneurons. These local circuit interactions may be critically involved in odor processing in vivo.

The vertebrate olfactory system must cope with a staggering developmental problem: how to connect millions of olfactory neurons expressing different odorant receptors to appropriate targets in the brain. Recent studies demonstrate remarkable plasticity in integrating novel olfactory sensory neurons into this circuitry.

Isaac Newton wrote that “We no other way know the extension of bodies than by our senses” (Principles Book III, rule III). This chapter will consider the ways we use our senses to know the extension of bodies and to further determine many other relevant dimensions of the world that we inhabit.

Phosphatidylinositol 3-kinase (PI3K)-dependent phosphoinositide signaling has been implicated in diverse cellular systems coupled to receptors for many different ligands, but the extent to which it functions in sensory transduction is yet to be determined. We now report that blocking PI3K activity increases odorant-evoked, cyclic nucleotide-dependent elevation of [Ca 2+ ] i in acutely dissociated rat olfactory receptor neurons and does so in an odorant-specific manner. These findings imply that 3-phosphoinositide signaling acts in vertebrate olfactory transduction to inhibit cyclic nucleotide-dependent excitation of the cells and that the interaction of the two signaling pathways is important in odorant coding, indicating that 3-phosphoinositide signaling can play a role in sensory transduction.

Research on lobster olfactory receptor cells has implicated a novel sodium-activated nonselective cation channel in olfactory transduction. In addition to providing some of the first evidence for a functional role for sodium-activated channels, these studies provide a possible explanation as to how the sensitivity of these channels to sodium could be much greater in intact cells than in excised patches.

The primary olfactory brain center, the antennal lobe (AL) in insects or the olfactory bulb in vertebrates, is a notable example of a neural network for sensory processing. While physiological properties of the input, the olfactory receptor neurons, have become clearer, the operation of the network itself remains cryptic. Therefore we measured spatio-temporal odor-response patterns in the output neurons of the olfactory glomeruli using optical imaging in the honeybee Apis mellifera. We mapped these responses to identified glomeruli, which are the structural and functional units of the AL. Each odor evoked a complex spatio-temporal activity pattern of excited and inhibited glomeruli. These properties were odor- and glomerulus-specific and were conserved across individuals. We compared the spatial pattern of excited glomeruli to previously published signals, which derived mainly from the receptor neurons, and found that they appeared more confined, showing that inhibitory connections enhance the contrast between glomeruli in the AL. To investigate the underlying mechanisms, we applied GABA and the GABA-receptor antagonist picrotoxin (PTX). The results show the presence of two separate inhibitory networks: one is GABAergic and modulates overall AL activity, the other is PTX-insensitive and glomerulus-specific. Inhibitory connections of the latter network selectively inhibit glomeruli with overlapping response profiles, in a way akin to “lateral” inhibition in other sensory systems. Selectively inhibited glomeruli need not be spatial neighbors. The net result is a globally modulated, contrast-enhanced and predictable representation of odors in the olfactory output neurons.

Synchronized firing of mitral cells (MCs) in the olfactory bulb (OB) has been hypothesized to help bind information together in olfactory cortex (OC). In this first survey of synchronized firing by suspected MCs in awake-behaving vertebrates we find the surprising result that synchronized firing conveys information on odor value (is it rewarded?) rather than odor identity (what is the odor?). We observed that as mice learned to discriminate between odors synchronous firing responses to the rewarded and unrewarded odors became divergent. Further, adrenergic blockage decreases the magnitude of odor divergence of synchronous trains suggesting that MCs contribute to decision-making through adrenergic-modulated synchronized firing. Thus, in the olfactory system information on stimulus reward is found in MCs one synapse away from the sensory neuron.

Two studies provide evidence for a critical period in the development of the olfactory system in mice.