PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (638066)

Clipboard (0)
None

Related Articles

1.  Olfactory Processing and Behavior Downstream from Highly Selective Receptor Neurons 
Nature neuroscience  2007;10(5):623-630.
In either the vertebrate nose or the insect antenna, most olfactory receptor neurons (ORNs) respond to multiple odors. However, some ORNs respond to just a single odor, or at most to a few highly related odors. It has been hypothesized that narrowly-tuned ORNs project to narrowly-tuned neurons in the brain, and that these dedicated circuits mediate innate behavioral responses to a particular ligand. Here we have investigated neural activity and behavior downstream from two narrowly-tuned ORN types in Drosophila. We found that genetically ablating either of these ORN types impairs innate behavioral attraction to their cognate ligand. Neurons in the antennal lobe postsynaptic to one of these ORN types are, like their presynaptic ORNs, narrowly tuned to a pheromone. However, neurons postsynaptic to the second ORN type are broadly tuned. These results demonstrate that some narrowly-tuned ORNs project to dedicated central circuits, ensuring a tight connection between stimulus and behavior, whereas others project to central neurons which participate in the ensemble representations of many odors.
doi:10.1038/nn1881
PMCID: PMC2838507  PMID: 17417635
2.  A Regulatory Code for Neuron-Specific Odor Receptor Expression 
PLoS Biology  2008;6(5):e125.
Olfactory receptor neurons (ORNs) must select—from a large repertoire—which odor receptors to express. In Drosophila, most ORNs express one of 60 Or genes, and most Or genes are expressed in a single ORN class in a process that produces a stereotyped receptor-to-neuron map. The construction of this map poses a problem of receptor gene regulation that is remarkable in its dimension and about which little is known. By using a phylogenetic approach and the genome sequences of 12 Drosophila species, we systematically identified regulatory elements that are evolutionarily conserved and specific for individual Or genes of the maxillary palp. Genetic analysis of these elements supports a model in which each receptor gene contains a zip code, consisting of elements that act positively to promote expression in a subset of ORN classes, and elements that restrict expression to a single ORN class. We identified a transcription factor, Scalloped, that mediates repression. Some elements are used in other chemosensory organs, and some are conserved upstream of axon-guidance genes. Surprisingly, the odor response spectra and organization of maxillary palp ORNs have been extremely well-conserved for tens of millions of years, even though the amino acid sequences of the receptors are not highly conserved. These results, taken together, define the logic by which individual ORNs in the maxillary palp select which odor receptors to express.
Author Summary
Odors are detected by olfactory receptor neurons (ORNs). Which odor an individual neuron detects is dictated by the odor receptors it expresses. Odor receptors are encoded by large families of genes, and an individual neuron must thus select the gene it expresses from among many possibilities. The mechanism underlying this choice is largely unknown. We have examined the problem of receptor gene choice in the fruit fly Drosophila, whose maxillary palp contains six functional classes of ORNs, each expressing different odor receptor genes. By comparing the DNA sequences flanking these genes in 12 different species of Drosophila, we have identified regulatory elements that are evolutionarily conserved and specific to each odor receptor. Genetic analysis of these elements showed that some act positively to dictate expression in a subset of ORNs, while others act negatively to restrict the expression of a receptor gene to a particular ORN class. We identified a transcription factor, Scalloped, that mediates repression. We were surprised to find that the odor response spectra of these neurons have been well-conserved for tens of millions of years, even though the amino acid sequences of their receptors have diverged considerably.
How does an olfactory receptor neuron select which odor receptor to express? A computational analysis of 12Drosophila genomes combined with mutational analysis identifies conservedcis elements and defines a regulatory code.
doi:10.1371/journal.pbio.0060125
PMCID: PMC2430909  PMID: 18846726
3.  Intensity invariant dynamics and odor-specific latencies in olfactory receptor neuron response 
Odors elicit spatio-temporal patterns of activity in the brain. Spatial patterns arise from the specificity of the interaction between odorants and odorant receptors expressed in different olfactory receptor neurons (ORNs). But the origin of temporal patterns of activity and their role in odor coding remain unclear. We investigate how physiological aspects of ORN response and physical aspects of odor stimuli give rise to diverse responses in Drosophila ORNs. We show that odor stimuli have intrinsic dynamics that depend on odor type and strongly affect ORN response. Using linear-nonlinear modeling to remove the contribution of the stimulus dynamics from the ORN dynamics we study the physiological properties of the response to different odorants and concentrations. For several odorants and receptor types the ORN response dynamics normalized by the peak response are independent of stimulus intensity for a large portion of the neuron’s dynamic range. Adaptation to a background odor changes the gain and dynamic range of the response but does not affect normalized response dynamics. Stimulating ORNs with various odorants reveals significant odor-dependent delays in the ORN response functions. These differences however can be dominated by differences in stimulus dynamics. In one case the response of one ORN to two odorants is predicted solely from measurements of the odor signals. Within a large portion of their dynamic range ORNs can capture information about stimulus dynamics independently from intensity while introducing odor-dependent delays. How insects might use odor-specific stimulus dynamics and ORN dynamics in discrimination and navigation tasks remains an open question.
doi:10.1523/JNEUROSCI.0426-12.2013
PMCID: PMC3678969  PMID: 23575828
4.  Asymmetric neurotransmitter release enables rapid odor lateralization in Drosophila 
Nature  2012;493(7432):424-428.
In Drosophila, most individual olfactory receptor neurons (ORNs) project bilaterally to both sides of the brain1,2. Having bilateral rather than unilateral projections may represent a useful redundancy. However, bilateral ORN projections to the brain should also compromise the ability to lateralize odors. Nevertheless, walking or flying Drosophila reportedly turn toward their more strongly stimulated antenna3-5. Here we show that each ORN spike releases ~40% more neurotransmitter from the axon branch ipsilateral to the soma, as compared to the contralateral branch. As a result, when an odor activates the antennae asymmetrically, ipsilateral central neurons begin to spike a few milliseconds before contralateral neurons, and ipsilateral central neurons also fire at a 30-50% higher rate. We show that a walking fly can detect a 5% asymmetry in total ORN input to its left and right antennal lobes, and can turn toward the odor in less time than it requires the fly to complete a stride. These results demonstrate that neurotransmitter release properties can be tuned independently at output synapses formed by a single axon onto two target cells with identical functions and morphologies. Our data also show that small differences in spike timing and spike rate can produce reliable differences in olfactory behavior.
doi:10.1038/nature11747
PMCID: PMC3590906  PMID: 23263180
5.  Sensory Processing in the Drosophila Antennal Lobe Increases the Reliability and Separability of Ensemble Odor Representations 
Nature neuroscience  2007;10(11):1474-1482.
Here we describe several fundamental principles of olfactory processing in the Drosophila antennal lobe (the analog of the vertebrate olfactory bulb), based on a systematic analysis of input and output spike trains of seven identified glomeruli. Repeated presentations of the same odor elicit more reproducible responses in second-order projection neurons (PNs) than in their presynaptic olfactory receptor neurons (ORNs). PN responses rise and accommodate rapidly, emphasizing odor onset. Furthermore, weak ORN inputs are amplified in the PN layer but strong inputs are not. This nonlinear transformation broadens PN tuning, and produces more uniform distances between odor representations in PN coding space. Additionally, a portion of a PN’s odor response profile is not systematically related to its direct ORN inputs, likely reflecting lateral connections between glomeruli. Finally, we show that a linear discriminator classifies odors more accurately using PN spike trains as compared to an equivalent number of ORN spike trains.
doi:10.1038/nn1976
PMCID: PMC2838615  PMID: 17922008
6.  A Presynaptic Gain Control Mechanism Fine-Tunes Olfactory Behavior 
Neuron  2008;59(2):311-321.
Early sensory processing can play a critical role in sensing environmental cues. We have investigated the physiological and behavioral function of gain control at the first synapse of olfactory processing in Drosophila. We report that olfactory receptor neurons (ORNs) express the GABAB receptor (GABABR) and its expression expands the dynamic range of ORN synaptic transmission that is preserved in projection neuron responses. Strikingly, we find that different ORN channels have unique baseline levels of GABABR expression. ORNs that sense the aversive odorant CO2 do not express GABABRs nor exhibit any presynaptic inhibition. In contrast, pheromone-sensing ORNs express a high level of GABABRs and exhibit strong presynaptic inhibition. Furthermore, a behavioral significance of presynaptic inhibition was revealed by a courtship behavior in which pheromone-dependent mate localization is impaired in flies that lack GABABRs in specific ORNs. Together, these findings indicate that different olfactory receptor channels may employ heterogeneous presynaptic gain control as a mechanism to allow an animal’s innate behavioral responses to match its ecological needs.
doi:10.1016/j.neuron.2008.07.003
PMCID: PMC2539065  PMID: 18667158
Drosophila; olfaction; GABAB; presynaptic inhibition; gain control; dynamic range; two-photon imaging
7.  Mechanisms of Maximum Information Preservation in the Drosophila Antennal Lobe 
PLoS ONE  2010;5(5):e10644.
We examined the presence of maximum information preservation, which may be a fundamental principle of information transmission in all sensory modalities, in the Drosophila antennal lobe using an experimentally grounded network model and physiological data. Recent studies have shown a nonlinear firing rate transformation between olfactory receptor neurons (ORNs) and second-order projection neurons (PNs). As a result, PNs can use their dynamic range more uniformly than ORNs in response to a diverse set of odors. Although this firing rate transformation is thought to assist the decoder in discriminating between odors, there are no comprehensive, quantitatively supported studies examining this notion. Therefore, we quantitatively investigated the efficiency of this firing rate transformation from the viewpoint of information preservation by computing the mutual information between odor stimuli and PN responses in our network model. In the Drosophila olfactory system, all ORNs and PNs are divided into unique functional processing units called glomeruli. The nonlinear transformation between ORNs and PNs is formed by intraglomerular transformation and interglomerular interaction through local neurons (LNs). By exploring possible nonlinear transformations produced by these two factors in our network model, we found that mutual information is maximized when a weak ORN input is preferentially amplified within a glomerulus and the net LN input to each glomerulus is inhibitory. It is noteworthy that this is the very combination observed experimentally. Furthermore, the shape of the resultant nonlinear transformation is similar to that observed experimentally. These results imply that information related to odor stimuli is almost maximally preserved in the Drosophila olfactory circuit. We also discuss how intraglomerular transformation and interglomerular inhibition combine to maximize mutual information.
doi:10.1371/journal.pone.0010644
PMCID: PMC2873944  PMID: 20502639
8.  Functional Roles for Synaptic-Depression within a Model of the Fly Antennal Lobe 
PLoS Computational Biology  2012;8(8):e1002622.
Several experiments indicate that there exists substantial synaptic-depression at the synapses between olfactory receptor neurons (ORNs) and neurons within the drosophila antenna lobe (AL). This synaptic-depression may be partly caused by vesicle-depletion, and partly caused by presynaptic-inhibition due to the activity of inhibitory local neurons within the AL. While it has been proposed that this synaptic-depression contributes to the nonlinear relationship between ORN and projection neuron (PN) firing-rates, the precise functional role of synaptic-depression at the ORN synapses is not yet fully understood. In this paper we propose two hypotheses linking the information-coding properties of the fly AL with the network mechanisms responsible for ORNAL synaptic-depression. Our first hypothesis is related to variance coding of ORN firing-rate information — once stimulation to the ORNs is sufficiently high to saturate glomerular responses, further stimulation of the ORNs increases the regularity of PN spiking activity while maintaining PN firing-rates. The second hypothesis proposes a tradeoff between spike-time reliability and coding-capacity governed by the relative contribution of vesicle-depletion and presynaptic-inhibition to ORNAL synaptic-depression. Synaptic-depression caused primarily by vesicle-depletion will give rise to a very reliable system, whereas an equivalent amount of synaptic-depression caused primarily by presynaptic-inhibition will give rise to a less reliable system that is more sensitive to small shifts in odor stimulation. These two hypotheses are substantiated by several small analyzable toy models of the fly AL, as well as a more physiologically realistic large-scale computational model of the fly AL involving glomerular channels.
Author Summary
Understanding the intricacies of sensory processing is a major scientific challenge. In this paper we examine the early stages of the olfactory system of the fruit-fly. Many experiments have revealed a great deal regarding the architecture of this system, including the types of neurons within it, as well as the connections those neurons make amongst one another. In this paper we examine the potential dynamics produced by this neuronal network. Specifically, we construct a computational model of this early olfactory system and study the effects of synaptic-depression within this system. We find that the dynamics and coding properties of this system depend strongly on the strength, and sources of, synaptic-depression. This work has ramifications for understanding the coding properties of other insect olfactory systems, and perhaps even other sensory modalities in other animals.
doi:10.1371/journal.pcbi.1002622
PMCID: PMC3426607  PMID: 22927802
9.  Ultrastructural localization of connexins (Cx36, Cx43, Cx45), glutamate receptors and aquaporin-4 in rodent olfactory mucosa, olfactory nerve and olfactory bulb 
Journal of neurocytology  2006;34(3-5):307-341.
Odorant/receptor binding and initial olfactory information processing occurs in olfactory receptor neurons (ORNs) within the olfactory epithelium. Subsequent information coding involves high-frequency spike synchronization of paired mitral/tufted cell dendrites within olfactory bulb (OB) glomeruli via positive feedback between glutamate receptors and closely-associated gap junctions. With mRNA for connexins Cx36, Cx43 and Cx45 detected within ORN somata and Cx36 and Cx43 proteins reported in ORN somata and axons, abundant gap junctions were proposed to couple ORNs. We used freeze-fracture replica immunogold labeling (FRIL) and confocal immunofluorescence microscopy to examine Cx36, Cx43 and Cx45 protein in gap junctions in olfactory mucosa, olfactory nerve and OB in adult rats and mice and early postnatal rats. In olfactory mucosa, Cx43 was detected in gap junctions between virtually all intrinsic cell types except ORNs and basal cells; whereas Cx45 was restricted to gap junctions in sustentacular cells. ORN axons contained neither gap junctions nor any of the three connexins. In OB, Cx43 was detected in homologous gap junctions between almost all cell types except neurons and oligodendrocytes. Cx36 and, less abundantly, Cx45 were present in neuronal gap junctions, primarily at “mixed” glutamatergic/electrical synapses between presumptive mitral/tufted cell dendrites. Genomic analysis revealed multiple miRNA (micro interfering RNA) binding sequences in 3′-untranslated regions of Cx36, Cx43 and Cx45 genes, consistent with cell-type-specific post-transcriptional regulation of connexin synthesis. Our data confirm absence of gap junctions between ORNs, and support Cx36- and Cx45-containing gap junctions at glutamatergic mixed synapses between mitral/tufted cells as contributing to higher-order information coding within OB glomeruli.
doi:10.1007/s11068-005-8360-2
PMCID: PMC1525003  PMID: 16841170
10.  Coding of odors by temporal binding within a model network of the locust antennal lobe 
The locust olfactory system interfaces with the external world through antennal receptor neurons (ORNs), which represent odors in a distributed, combinatorial manner. ORN axons bundle together to form the antennal nerve, which relays sensory information centrally to the antennal lobe (AL). Within the AL, an odor generates a dynamically evolving ensemble of active cells, leading to a stimulus-specific temporal progression of neuronal spiking. This experimental observation has led to the hypothesis that an odor is encoded within the AL by a dynamically evolving trajectory of projection neuron (PN) activity that can be decoded piecewise to ascertain odor identity. In order to study information coding within the locust AL, we developed a scaled-down model of the locust AL using Hodgkin–Huxley-type neurons and biologically realistic connectivity parameters and current components. Using our model, we examined correlations in the precise timing of spikes across multiple neurons, and our results suggest an alternative to the dynamic trajectory hypothesis. We propose that the dynamical interplay of fast and slow inhibition within the locust AL induces temporally stable correlations in the spiking activity of an odor-dependent neural subset, giving rise to a temporal binding code that allows rapid stimulus detection by downstream elements.
doi:10.3389/fncom.2013.00050
PMCID: PMC3635028  PMID: 23630495
antennal lobe; temporal binding; computational neuroscience; odor coding; slow temporal patterns; oscillations; synchrony; time scales of inhibition
11.  An RNA-Seq Screen of the Drosophila Antenna Identifies a Transporter Necessary for Ammonia Detection 
PLoS Genetics  2014;10(11):e1004810.
Many insect vectors of disease detect their hosts through olfactory cues, and thus it is of great interest to understand better how odors are encoded. However, little is known about the molecular underpinnings that support the unique function of coeloconic sensilla, an ancient and conserved class of sensilla that detect amines and acids, including components of human odor that are cues for many insect vectors. Here, we generate antennal transcriptome databases both for wild type Drosophila and for a mutant that lacks coeloconic sensilla. We use these resources to identify genes whose expression is highly enriched in coeloconic sensilla, including many genes not previously implicated in olfaction. Among them, we identify an ammonium transporter gene that is essential for ammonia responses in a class of coeloconic olfactory receptor neurons (ORNs), but is not required for responses to other odorants. Surprisingly, the transporter is not expressed in ORNs, but rather in neighboring auxiliary cells. Thus, our data reveal an unexpected non-cell autonomous role for a component that is essential to the olfactory response to ammonia. The defective response observed in a Drosophila mutant of this gene is rescued by its Anopheles ortholog, and orthologs are found in virtually all insect species examined, suggesting that its role is conserved. Taken together, our results provide a quantitative analysis of gene expression in the primary olfactory organ of Drosophila, identify molecular components of an ancient class of olfactory sensilla, and reveal that auxiliary cells, and not simply ORNs, play an essential role in the coding of an odor that is a critical host cue for many insect vectors of human disease.
Author Summary
Olfaction underlies the attraction of insect pests and vectors of disease to their plant and human hosts. In the genetic model insect Drosophila, the neuronal basis of odor coding has been extensively analyzed in the antenna, its major olfactory organ, but the molecular basis of odor coding has not. Additionally, there has been little analysis of any olfactory cells other than neurons. We have undertaken a comprehensive and quantitative analysis of gene expression in the Drosophila antenna. This analysis revealed a surprisingly broad dynamic range of odor receptor and odor binding protein expression, and unexpected expression of taste receptor genes. Further analysis identified 250 genes that are expressed at reduced levels in a mutant lacking an evolutionarily ancient class of sensilla, antennal hairs housing neurons that respond to human odors. One of these genes, a transporter, is expressed in non-neuronal cells but is essential to the response of a neuron to ammonia, a key cue for insect vectors of disease. A mutation in this transporter can be rescued by its mosquito homolog. While many studies of sensory coding consider the neural circuit in isolation, our analysis reveals an essential role for an auxiliary cell.
doi:10.1371/journal.pgen.1004810
PMCID: PMC4238959  PMID: 25412082
12.  Activation of Glial FGFRs Is Essential in Glial Migration, Proliferation, and Survival and in Glia-Neuron Signaling during Olfactory System Development 
PLoS ONE  2012;7(4):e33828.
Development of the adult olfactory system of the moth Manduca sexta depends on reciprocal interactions between olfactory receptor neuron (ORN) axons growing in from the periphery and centrally-derived glial cells. Early-arriving ORN axons induce a subset of glial cells to proliferate and migrate to form an axon-sorting zone, in which later-arriving ORN axons will change their axonal neighbors and change their direction of outgrowth in order to travel with like axons to their target areas in the olfactory (antennal) lobe. These newly fasciculated axon bundles will terminate in protoglomeruli, the formation of which induces other glial cells to migrate to surround them. Glial cells do not migrate unless ORN axons are present, axons fail to fasciculate and target correctly without sufficient glial cells, and protoglomeruli are not maintained without a glial surround. We have shown previously that Epidermal Growth Factor receptors and the IgCAMs Neuroglian and Fasciclin II play a role in the ORN responses to glial cells. In the present work, we present evidence for the importance of glial Fibroblast Growth Factor receptors in glial migration, proliferation, and survival in this developing pathway. We also report changes in growth patterns of ORN axons and of the dendrites of olfactory (antennal lobe) neurons following blockade of glial FGFR activation that suggest that glial FGFR activation is important in reciprocal communication between neurons and glial cells.
doi:10.1371/journal.pone.0033828
PMCID: PMC3320908  PMID: 22493675
13.  Olfactory subsystems in the honeybee: sensory supply and sex specificity 
Cell and Tissue Research  2014;357(3):583-595.
The antennae of honeybee (Apis mellifera) workers and drones differ in various aspects. One striking difference is the presence of Sensilla basiconica in (female) workers and their absence in (male) drones. We investigate the axonal projection patterns of olfactory receptor neurons (ORNs) housed in S. basiconica in honeybee workers by using selective anterograde labeling with fluorescent tracers and confocal-microscopy analysis of axonal projections in antennal lobe glomeruli. Axons of S. basiconica-associated ORNs preferentially projected into a specific glomerular cluster in the antennal lobe, namely the sensory input-tract three (T3) cluster. T3-associated glomeruli had previously been shown to be innervated by uniglomerular projection (output) neurons of the medial antennal lobe tract (mALT). As the number of T3 glomeruli is reduced in drones, we wished to determine whether this was associated with the reduction of glomeruli innervated by medial-tract projection neurons. We retrogradely traced mALT projection neurons in drones and counted the innervated glomeruli. The number of mALT-associated glomeruli was strongly reduced in drones compared with workers. The preferential projections of S. basiconica-associated ORNs in T3 glomeruli together with the reduction of mALT-associated glomeruli support the presence of a female (worker)-specific olfactory subsystem that is partly innervated by ORNs from S. basiconica and is associated with the T3 cluster of glomeruli and mALT projection neurons. We propose that this olfactory subsystem supports parallel olfactory processing related to worker-specific olfactory tasks such as the coding of colony odors, colony pheromones and/or odorants associated with foraging on floral resources.
Electronic supplementary material
The online version of this article (doi:10.1007/s00441-014-1892-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s00441-014-1892-y
PMCID: PMC4148592  PMID: 24817103
Sensilla basiconica; Antennal lobe; Glomeruli; Projection neuron; Honeybee drone
14.  PROTEOGLYCAN ABNORMALITIES IN OLFACTORY EPITHELIUM TISSUE FROM SUBJECTS DIAGNOSED WITH SCHIZOPHRENIA 
Schizophrenia research  2013;150(0):366-372.
Emerging evidence points to proteoglycans abnormalities in the pathophysiology of schizophrenia (SZ). In particular, markedly abnormal expression of chondroitin sulfate proteoglycans (CSPGs), key components of the extracellular matrix, was observed in the medial temporal lobe. CSPG functions, including regulation of neuronal differentiation and migration, are highly relevant to the pathophysiology of SZ. CSPGs may exert similar functions in the olfactory epithelium (OE), a continuously regenerating neural tissue that shows cell and molecular abnormalities in SZ. We tested the hypothesis that CSPG expression in OE may be altered in SZ. CSPG-positive cells in postmortem OE from nonpsychiatric control (n=9) and SZ (n=10) subjects were counted using computer-assisted light microscopy. ‘Cytoplasmic’ CSPG (c-CSPG) labeling was detected in sustentacular cells and some olfactory receptor neurons (c-CSPG+ORNs), while ‘pericellular’ CSPG (p-CSPG) labeling was found in basal cells and some ORNs (p-CSPG+ORNs). Dual labeling for CSPG and markers for mature and immature ORNs suggests that c-CSPG+ORNs correspond to mature ORNs, and p-CSPG+ORNs to immature ORNs. Previous studies in the same cohort demonstrated that densities of mature ORNs were unaltered (Arnold et al, 2001). In the present study, numerical densities of c-CSPG+ORNs were significantly decreased in SZ (p <0.025; 99.32% decrease), suggesting a reduction of CSPG expression in mature ORNs. Previous studies showed a striking increase in the ratios of immature neurons with respect to basal cells. In this study, we find that the ratio of p-CSPG+ORNs/ CSPG+ basal cells was significantly increased (p=0.03) in SZ, while numerical density changes of p-CSPG+ORNs (110.71% increase) or CSPG+ basal cells (53.71% decrease), did not reach statistical significance. Together, these results indicate that CSPG abnormalities are present in the OE of SZ and specifically point to a reduction of CSPGs expression in mature ORNs in SZ. Given the role CSPG play in OE cell differentiation and axon guidance, we suggest that altered CSPG expression may contribute to ORN lineage dysregulation, and olfactory identification abnormalities, observed in SZ.
doi:10.1016/j.schres.2013.08.013
PMCID: PMC4215560  PMID: 24035561
Schizophrenia; extracellular matrix; chondroitin sulfate proteoglycans; olfactory epitheliu; postmortem
15.  Temporally diverse firing patterns in olfactory receptor neurons underlie spatiotemporal neural codes for odors 
Odorants are represented as spatiotemporal patterns of spikes in neurons of the antennal lobe (AL, insects) and olfactory bulb (OB, vertebrates). These response patterns have been thought to arise primarily from interactions within the AL/OB, an idea supported, in part, by the assumption that olfactory receptor neurons (ORNs) respond to odorants with simple firing patterns. However, activating the AL directly with simple pulses of current evoked responses in AL neurons that were much less diverse, complex, and enduring than responses elicited by odorants. Similarly, models of the AL driven by simplistic inputs generated relatively simple output. How then are dynamic neural codes for odors generated? Consistent with recent results from several other species, our recordings from locust ORNs showed a great diversity of temporal structure. Further, we found that, viewed as a population, many response features of ORNs were remarkably similar to those observed within the AL. Using a set of computational models constrained by our electrophysiological recordings, we found that the temporal heterogeneity of responses of ORNs critically underlies the generation of spatiotemporal odor codes in the AL. A test then performed in vivo confirmed that, given temporally homogeneous input, the AL cannot create diverse spatiotemporal patterns on its own; however, given temporally heterogeneous input, the AL generated realistic firing patterns. Finally, given the temporally structured input provided by ORNs, we clarified several separate, additional contributions of the AL to olfactory information processing. Thus, our results demonstrate the origin and subsequent reformatting of spatiotemporal neural codes for odors.
doi:10.1523/JNEUROSCI.5639-09.2010
PMCID: PMC2835415  PMID: 20147528
temporal; spike trains; sensory neurons; chemosensory; input; interneurons; antenna
16.  Apis mellifera octopamine receptor 1 (AmOA1) expression in antennal lobe networks of the honey bee (Apis mellifera) and fruit fly (Drosophila melanogaster) 
Octopamine (OA) underlies reinforcement during appetitive conditioning in the honey bee and fruit fly, acting via different subtypes of receptors. Recently, antibodies raised against a peptide sequence of one honey bee OA receptor, AmOA1, were used to study the distribution of these receptors in the honey bee brain (Sinakevitch et al., 2011). These antibodies also recognize an isoform of the AmOA1 ortholog in the fruit fly (OAMB, mushroom body OA receptor). Here we describe in detail the distribution of AmOA1 receptors in different types of neurons in the honey bee and fruit fly antennal lobes. We integrate this information into a detailed anatomical analysis of olfactory receptor neurons (ORNs), uni- and multi-glomerular projection neurons (uPNs, and mPNs) and local interneurons (LNs) in glomeruli of the antennal lobe. These neurons were revealed by dye injection into the antennal nerve, antennal lobe, medial and lateral antenno-protocerbral tracts (m-APT and l-APT), and lateral protocerebral lobe (LPL) by use of labeled cell lines in the fruit fly or by staining with anti-GABA. We found that ORN receptor terminals and uPNs largely do not show immunostaining for AmOA1. About seventeen GABAergic mPNs leave the antennal lobe through the ml-APT and branch into the LPL. Many, but not all, mPNs show staining for AmOA1. AmOA1 receptors are also in glomeruli on GABAergic processes associated with LNs. The data suggest that in both species one important action of OA in the antennal lobe involves modulation of different types of inhibitory neurons via AmOA1 receptors. We integrated this new information into a model of circuitry within glomeruli of the antennal lobes of these species.
doi:10.3389/fnsys.2013.00070
PMCID: PMC3807565  PMID: 24187534
biogenic amine receptors; G-protein receptors; octopamine; learning and plasticity; olfactory pathways
17.  Imaging ensemble activity in arthropod olfactory receptor neurons in situ 
Cell calcium  2011;49(2):100-107.
We show that lobster olfactory receptor neurons (ORNs), much like their vertebrate counterparts, generate a transient elevation of intracellular calcium (Cai) in response to odorant activation that can be used to monitor ensemble ORN activity. This is done in antennal slice preparation in situ maintaining the polarity of the cells and the normal micro-environment of the olfactory ilia. The Cai signal is ligand-specific and increases in a dose-dependent manner in response to odorant stimulation. Saturating stimulation elicits a robust increase of up to 1 μM free Cai within 1–2 sec of stimulation. The odor-induced Cai response closely follows the discharge pattern of extracellular spikes elicited by odorant application, with the maximal rise in Cai matching the peak of the spike generation. The Cai signal can be used to track neuronal activity in a functional subpopulation of rhythmically active ORNs and discriminate it from that of neighboring tonically active ORNs. Being able to record from many ORNs simultaneously over an extended period of time not only allows more accurate estimates of neuronal population activity but also dramatically improves the ability to identify potential new functional subpopulations of ORNs, especially those with more subtle differences in responsiveness, ligand specificity, and/or transduction mechanisms.
doi:10.1016/j.ceca.2010.10.009
PMCID: PMC3050052  PMID: 21232792
18.  Synaptic organization of the Drosophila antennal lobe and its regulation by the Teneurins 
eLife  2014;3:e03726.
Understanding information flow through neuronal circuits requires knowledge of their synaptic organization. In this study, we utilized fluorescent pre- and postsynaptic markers to map synaptic organization in the Drosophila antennal lobe, the first olfactory processing center. Olfactory receptor neurons (ORNs) produce a constant synaptic density across different glomeruli. Each ORN within a class contributes nearly identical active zone number. Active zones from ORNs, projection neurons (PNs), and local interneurons have distinct subglomerular and subcellular distributions. The correct number of ORN active zones and PN acetylcholine receptor clusters requires the Teneurins, conserved transmembrane proteins involved in neuromuscular synapse organization and synaptic partner matching. Ten-a acts in ORNs to organize presynaptic active zones via the spectrin cytoskeleton. Ten-m acts in PNs autonomously to regulate acetylcholine receptor cluster number and transsynaptically to regulate ORN active zone number. These studies advanced our ability to assess synaptic architecture in complex CNS circuits and their underlying molecular mechanisms.
DOI: http://dx.doi.org/10.7554/eLife.03726.001
eLife digest
Just as progress in science relies on researchers communicating their findings to other people working in their field, our bodies rely on neurons being able to communicate with other neurons. This is where structures called synapses come in: synapses allow signals to be passed from one neuron to another. Neurons and synapses process information by forming circuits in the brain, but relatively little is known about how synapses develop or how they are organized within circuits.
Mosca and Luo have now examined a neural circuit in the fruit fly (Drosophila) that receives sensory information about smells in the environment, and then converts this information to signals which can be understood by other parts of the brain. This particular circuit has previously been identified as a good model of how the brain processes information.
Mosca and Luo found that the synapses in this circuit were organized according to specific ‘rules’ that determined factors such as the quantity and location of synapses at different points in the circuit. Additionally, it was found that the successful development of synapses required the involvement of two members of a family of proteins called the Teneurins: this family of proteins is involved in a variety of neurodevelopmental processes.
Teneurins have been implicated in bipolar disorder, and malfunctioning synapses are thought to be associated with a number of other mental health conditions, so the results of Mosca and Luo could lead to a better understanding of these conditions.
DOI: http://dx.doi.org/10.7554/eLife.03726.002
doi:10.7554/eLife.03726
PMCID: PMC4194450  PMID: 25310239
synapse; olfaction; Teneurin; antennal lobe; drosophila; D. melanogaster
19.  Excitatory Local Circuits and Their Implications for Olfactory Processing in the Fly Antennal Lobe 
Cell  2007;128(3):601-612.
Summary
Conflicting views exist of how circuits of the antennal lobe, the insect equivalent of the olfactory bulb, translate input from olfactory receptor neurons (ORNs) into projection neuron (PN) output. Synaptic connections between ORNs and PNs are one-to-one, yet PNs are more broadly tuned to odors than ORNs. The basis for this difference in receptive range remains unknown. Analyzing a Drosophila mutant lacking ORN input to one glomerulus, we show that some of the apparent complexity in the antennal lobe’s output arises from lateral, interglomerular excitation of PNs. We describe a previously unidentified population of cholinergic local neurons (LNs) with multiglomerular processes. These excitatory LNs respond broadly to odors but exhibit little glomerular specificity in their synaptic output, suggesting that PNs are driven by a combination of glomerulus-specific ORN afferents and diffuse LN excitation. Lateral excitation may boost PN signals and enhance their transmission to third-order neurons in a mechanism akin to stochastic resonance.
doi:10.1016/j.cell.2006.12.034
PMCID: PMC2866183  PMID: 17289577
20.  Functional classification and central nervous projections of olfactory receptor neurons housed in antennal trichoid sensilla of female yellow fever mosquitoes, Aedes aegypti 
The European Journal of Neuroscience  2007;26(6):1611-1623.
Mosquitoes are highly dependent on their olfactory system for, e.g. host location and identification of nectar-feeding and oviposition sites. Odours are detected by olfactory receptor neurons (ORNs) housed in hair-shaped structures, sensilla, on the antennae and maxillary palps. In order to unravel the function of the olfactory system in the yellow fever vector, Aedes aegypti, we performed single-sensillum recordings from trichoid sensilla on female antennae. These sensilla are divided into four distinct morphological types. Based on the response to a set of 16 odour compounds, we identified 18 different ORN types, housed in 10 sensillum types. The ORNs responded to behaviourally relevant olfactory cues, such as oviposition attractants and sweat-borne compounds, including 4-methylcyclohexanol and indole, respectively. Two ORNs housed in these sensilla, as well as two ORNs housed in an additional sensillum type, did not respond to any of the compounds tested. The ORNs housed in individual sensilla exhibited stereotypical pairing and displayed differences in signalling mode (excitatory and inhibitory) as well as in temporal response patterns. In addition to physiological characterization, we performed anterograde neurobiotin stainings of functionally identified ORNs in order to define the functional map among olfactory glomeruli in the primary olfactory centre, the antennal lobe. The targeted glomeruli were compared with an established 3D map. Our data showed that the ORN types sent their axons to defined antennal lobe glomeruli in a stereotypic pattern.
doi:10.1111/j.1460-9568.2007.05786.x
PMCID: PMC2121139  PMID: 17880395
Aedes aegypti; antennal sensilla; olfaction; ORNs; physiology
21.  Differentially Expressed Drl and Drl-2 Play Opposing Roles in Wnt5 Signaling during Drosophila Olfactory System Development 
In Drosophila, odor information received by olfactory receptor neurons (ORNs) is processed by glomeruli, which are organized in a stereotypic manner in the antennal lobe (AL). This glomerular organization is regulated by Wnt5 signaling. In the embryonic CNS, Wnt5 signaling is transduced by the Drl receptor, a member of the Ryk family. During development of the olfactory system, however, it is antagonized by Drl. Here, we identify Drl-2 as a receptor mediating Wnt5 signaling. Drl is found in the neurites of brain cells in the AL and specific glia, whereas Drl-2 is predominantly found in subsets of growing ORN axons. A drl-2 mutation produces only mild deficits in glomerular patterning, but when it is combined with a drl mutation, the phenotype is exacerbated and more closely resembles the Wnt5 phenotype. Wnt5 overexpression in ORNs induces aberrant glomeruli positioning. This phenotype is ameliorated in the drl-2 mutant background, indicating that Drl-2 mediates Wnt5 signaling. In contrast, forced expression of Drl-2 in the glia of drl mutants rescues the glomerular phenotype caused by the loss of antagonistic Drl function. Therefore, Drl-2 can also antagonize Wnt5 signaling. Additionally, our genetic data suggest that Drl localized to developing glomeruli mediates Wnt5 signaling. Thus, these two members of the Ryk family are capable of carrying out a similar molecular function, but they can play opposing roles in Wnt5 signaling, depending on the type of cells in which they are expressed. These molecules work cooperatively to establish the olfactory circuitry in Drosophila.
doi:10.1523/JNEUROSCI.2821-08.2009
PMCID: PMC2749065  PMID: 19369566
22.  Homeostatic matching and nonlinear amplification at identified central synapses 
Neuron  2008;58(3):401-413.
SUMMARY
Here we describe the properties of an identified synapse in the Drosophila antennal lobe, and show how they can explain specific in vivo sensory computations in this brain region. The synapse between olfactory receptor neurons (ORNs) and projection neurons (PNs) is very strong, reflecting a large number of vesicular release sites and a high release probability. This is likely one reason why weak ORN odor responses are amplified in PNs. Furthermore, the amplitude of the unitary synaptic current in a PN is matched to the size of its dendritic arbor. This matching may compensate for a lower input resistance of larger PN dendrites to produce uniform depolarization across PN types. Consistent with this idea, a genetic manipulation which lowers PN input resistance produces larger unitary synaptic currents. Finally, strong stimuli produce short-term depression at this synapse. This helps explain why PN odor responses are transient, and why strong ORN odor responses are not amplified as powerfully as weak responses.
doi:10.1016/j.neuron.2008.02.030
PMCID: PMC2429849  PMID: 18466750
23.  DSL-Notch signaling in the Drosophila brain in response to olfactory stimulation 
Neuron  2011;69(3):468-481.
Summary
Delta/Serrate/Lag2 (DSL) ligands and their Notch family receptors have profound and pervasive roles in development. They are also expressed in adult tissues, notably in mature neurons and glia in the brain, where their roles are unknown. Here, focusing on the sense of smell in adult Drosophila, we show that Notch is activated in select olfactory receptor neurons (ORNs) in an odorant specific fashion. This response requires olfactory receptor activity and the Notch ligand Delta. We present evidence that Notch activation depends on synaptic transmission by the ORNs in which the receptors are active, and is modulated by the activity of local interneurons in the antennal lobe. It is also subject to regulatory inputs from olfactory receptor activity in other ORNs. These findings identify a new correlate of stimulus-dependent brain activity, and potentially new forms of neural integration and plasticity.
doi:10.1016/j.neuron.2010.12.015
PMCID: PMC3216490  PMID: 21315258
24.  Excitatory Local Interneurons Enhance Tuning of Sensory Information 
PLoS Computational Biology  2012;8(7):e1002563.
Neurons in the insect antennal lobe represent odors as spatiotemporal patterns of activity that unfold over multiple time scales. As these patterns unspool they decrease the overlap between odor representations and thereby increase the ability of the olfactory system to discriminate odors. Using a realistic model of the insect antennal lobe we examined two competing components of this process –lateral excitation from local excitatory interneurons, and slow inhibition from local inhibitory interneurons. We found that lateral excitation amplified differences between representations of similar odors by recruiting projection neurons that did not receive direct input from olfactory receptors. However, this increased sensitivity also amplified noisy variations in input and compromised the ability of the system to respond reliably to multiple presentations of the same odor. Slow inhibition curtailed the spread of projection neuron activity and increased response reliability. These competing influences must be finely balanced in order to decorrelate odor representations.
Author Summary
The antennal lobe of insects and the olfactory bulb of vertebrates represent the first centers of the olfactory system where information about odor properties can be reorganized and optimized for further processing. Complex excitatory and inhibitory synaptic interactions within the antennal lobe and the olfactory bulb alter the responses of the principal neurons throughout the duration of the odor stimulation. These dynamic changes progressively increase the difference between firing patterns evoked by structurally similar odors, potentially helping the animal distinguish one odor from another. However, this process, called odor decorrelation, appears to oppose another important goal of olfactory processing, to minimize the inevitable noisy variations in representations of the same odor encountered under different environmental conditions; such variations could potentially lead to misclassification. It remains an interesting mystery how olfactory circuitry can solve these two seemingly contradictory goals as they process olfactory stimuli: first, separating different but chemically similar odors (sensitivity, capacity); and second, identifying representations of the same odor in a noisy environment (reliability). Our results suggest a balance between inhibitory and excitatory connections mediated by local antennal lobe interneurons enhances the decorrelation of similar odors while keeping the representation robust in the presence of noise.
doi:10.1371/journal.pcbi.1002563
PMCID: PMC3395596  PMID: 22807661
25.  Odor Evoked Neural Oscillations in Drosophila Are Mediated by Widely Branching Interneurons 
Stimulus-evoked oscillatory synchronization of neurons has been observed in a wide range of species. Here, we combined genetic strategies with paired intracellular and local field potential (LFP) recordings from the intact brain of Drosophila to study mechanisms of odor-evoked neural oscillations. We found common food odors at natural concentrations elicited oscillations in LFP recordings made from the mushroom body (MB), a site of sensory integration and analogous to the vertebrate pyriform cortex. The oscillations were reversibly abolished by application of the GABAa blocker picrotoxin. Intracellular recordings from local and projection neurons within the antennal lobe (AL, analogous to the olfactory bulb) revealed odor-elicited spikes and sub-threshold membrane potential oscillations that were tightly phase-locked to LFP oscillations recorded downstream in the MBs. These results suggested that, as in locusts, odors may elicit the oscillatory synchronization of AL neurons by means of GABAergic inhibition from local neurons (LNs). An analysis of the morphologies of genetically distinguished LNs revealed two populations of GABAergic neurons in the AL. One population of LNs innervated parts of glomeruli lacking terminals of receptor neurons, whereas the other branched more widely, innervating throughout the glomeruli, suggesting the two populations might participate in different neural circuits. To test the functional roles of these LNs, we used the temperature-sensitive dynamin mutant gene, shibire, to conditionally and reversibly block chemical transmission from each or both of these populations of LNs. We found only the more widely branching population of LNs is necessary for generating odor-elicited oscillations.
doi:10.1523/JNEUROSCI.1455-09.2009
PMCID: PMC2753235  PMID: 19571150
antennal lobe; local neuron; mushroom body; olfaction; coding; synchrony

Results 1-25 (638066)