Understanding neuronal representations of odor-evoked activities and their progressive transforma... more Understanding neuronal representations of odor-evoked activities and their progressive transformation from the sensory level to higher brain centers features one of the major aims in olfactory neuroscience. Here, we investigated how odor information is transformed and represented in higher-order neurons of the lateral horn, one of the higher olfactory centers implicated in determining innate behavior, using Drosophila melanogaster. We focused on a subset of third-order glutamatergic lateral horn neurons (LHNs) and characterized their odor coding properties in relation to their presynaptic partner neurons, the projection neurons (PNs) by two-photon functional imaging. We show that odors evoke reproducible, stereotypic, and odor-specific response patterns in LHNs. Notably, odor-evoked responses in these neurons are valence-specific in a way that their response amplitude is positively correlated with innate odor preferences. We postulate that this valence-specific activity is the resul...
Two families of ligand-gated ion channels function as olfactory receptors in insects. Here, we sh... more Two families of ligand-gated ion channels function as olfactory receptors in insects. Here, we show that these canonical olfactory receptors are not necessary for responses to ammonia, a key ecological odor that is attractive to many insects including disease vectors and agricultural pests. Instead, we show that a member of the ancient electrogenic ammonium transporter family, Amt, is a new type of olfactory receptor. We report two hitherto unidentified olfactory neuron populations that mediate neuronal and behavioral responses to ammonia. Their endogenous ammonia responses are Amt-dependent, and ectopic expression of either Drosophila or Anopheles Amt confers ammonia sensitivity. Amt is the first transporter known to function as an olfactory receptor in animals, and its role may be conserved across insect species.
The study of sensory systems in insects has a long-spanning history of almost an entire century. ... more The study of sensory systems in insects has a long-spanning history of almost an entire century. Olfaction, vision, and gustation are thoroughly researched in several robust insect models and new discoveries are made every day on the more elusive thermo- and mechano-sensory systems. Few specialized senses such as hygro- and magneto-reception are also identified in some insects. In light of recent advancements in the scientific investigation of insect behavior, it is not only important to study sensory modalities individually, but also as a combination of multimodal inputs. This is of particular significance, as a combinatorial approach to study sensory behaviors mimics the real-time environment of an insect with a wide spectrum of information available to it. As a fascinating field that is recently gaining new insight, multimodal integration in insects serves as a fundamental basis to understand complex insect behaviors including, but not limited to navigation, foraging, learning, a...
Inter-individual differences in behavioral responses, anatomy or functional properties of neurona... more Inter-individual differences in behavioral responses, anatomy or functional properties of neuronal populations of animals having the same genotype were for a long time disregarded. The majority of behavioral studies were conducted at a group level, and usually the mean behavior of all individuals was considered. Similarly, in neurophysiological studies, data were pooled and normalized from several individuals. This approach is mostly suited to map and characterize stereotyped neuronal properties between individuals, but lacks the ability to depict inter-individual variability regarding neuronal wiring or physiological characteristics. Recent studies have shown that behavioral biases and preferences to olfactory stimuli can vary significantly among individuals of the same genotype. The origin and the benefit of these diverse “personalities” is still unclear and needs to be further investigated. A perspective taken into account the inter-individual differences is needed to explore the...
Additional file 6: Figure S3. of Olfactory coding from the periphery to higher brain centers in the Drosophila brain
Correlation between glomerular distance and PN odor response similarity. Scatterplot of anatomica... more Correlation between glomerular distance and PN odor response similarity. Scatterplot of anatomical glomerular distance versus PN response distance for all 465 pairwise combinations of the 31 glomeruli. Pairwise distance of PN response distance was calculated based on odor response of 31 PN classes using cosine distances for 17 odors. (PDF 740 kb)
Additional file 12: Figure S9. of Olfactory coding from the periphery to higher brain centers in the Drosophila brain
Temporal dynamics of odor representation. (a) Represented trajectories of PN ensemble activities ... more Temporal dynamics of odor representation. (a) Represented trajectories of PN ensemble activities for three odors (red: ethyl butyrate, blue: acetophenone, green: 1-octen-3-ol) visualized in the three-dimensional PC space. Color is matched with Fig. 4a. Each trajectory is reconstructed with 100-ms steps indicated with circles, and filled circles indicate 150, 450, and 950-ms time frames. (b) Two-dimensional view of the odor response trajectories for all odors. The odors within the same cluster (colored in red, blue, green, and gray) in Fig. 4a have similar trajectories compared to those between different clusters. (c) Inter-odor distances between pairs of odors measured by ensemble PN odor responses with Euclidean distances. (d) Distance matrices of odor representations by PNs at different time frames. Odors are ordered in the same order as in Fig. 4b, to facilitate comparison to the pattern reconstructed with the mean firing rate for 1-s odor stimuli. Clustering of odors remain larg...
Additional file 11: Figure S8. of Olfactory coding from the periphery to higher brain centers in the Drosophila brain
Axonal density maps of PNs in the LH and in the MB. (a) Hierarchical cluster analysis for 28 PN c... more Axonal density maps of PNs in the LH and in the MB. (a) Hierarchical cluster analysis for 28 PN classes based on the correlation distances between axonal density maps in the LH. (b) Hierarchical cluster analysis for 28 PN classes based on the correlation distances between axonal density maps in the MB. (c) The density maps of axonal projections of each PN class are visualized two-dimensionally in the LH. The pseudo color for each PN is scaled respectively. (d) The density maps of axonal projections of each PN class are visualized two-dimensionally in the MB. The pseudo color for each PN is scaled respectively. (PDF 755 kb)
Additional file 8: Figure S5. of Olfactory coding from the periphery to higher brain centers in the Drosophila brain
Physicochemical properties of odors partly correlate with AL odor representation. (a) Hierarchica... more Physicochemical properties of odors partly correlate with AL odor representation. (a) Hierarchical cluster analysis for the 16 odors (except for geosmin, due to no data available) based on the Euclidean distances between physicochemical properties of the 16 odors. Glomerular names are colored according to the three clusters found in Fig. 4a, to facilitate comparison between these two analyses. (b) A complete distance matrix measured with Euclidean distances for 16 odors based on physicochemical properties. Each axis of the matrix is ordered as in (a). (c) Principal component analyses for the 16 odors based on physicochemical properties. The percentages of variance accounted by each PC component are shown on each axis. (d) Scatterplot of physicochemical distance versus PN response distance for all 120 pairwise combinations of the 16 odors. Pairwise distance of odors based on PN odor responses was calculated as in Fig. 4b. (PDF 762 kb)
Additional file 10: Figure S7. of Olfactory coding from the periphery to higher brain centers in the Drosophila brain
Axonal projections of PNs in the LH and in the MB. (a) The position of glomeruli are mapped on a ... more Axonal projections of PNs in the LH and in the MB. (a) The position of glomeruli are mapped on a template AL. (b) Reconstructed axonal projections in the MB calyx and LH. The PNs are labeled with the same color scheme as in (a). (c) Individual traces of reconstructed axonal projections for the 28 PN classes after registration to the template MB calyx and LH. PNs and glomeruli are colored according to the clusters in Fig. 4c, except for VM2 (magenta), which is included in all the three clusters, and D, DM6 (cyan), which are included in the second and third clusters. Anterior view (top) and dorsal view (bottom). Scale bars = 50 μm. (PDF 43110 kb)
Ó The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Dro... more Ó The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Drosophila melanogaster is today one of the three foremost models in olfactory research, paralleled only by the mouse and the nematode. In the last years, immense progress has been achieved by combining neurogenetic tools with neurophysiology, anatomy, chemistry, and behavioral assays. One of the most important tasks for a fruit fly is to find a substrate for eating and laying eggs. To perform this task the fly is dependent on olfactory cues emitted by suitable substrates as e.g. decaying fruit. In addition, in this area, considerable progress has been made during the last years, and more and more natural and behaviorally active ligands have been identified. The future challenge is to tie the progress in different fields together to give us a better understanding of how a fly really behaves. Not in a test tube, but in nature. Here, we review our present state of knowledge regarding Drosophi...
Uncovering how the lPBN is modulated by metabolism, physiology, and emotional states will help sh... more Uncovering how the lPBN is modulated by metabolism, physiology, and emotional states will help shed light on how context modulates what we find painful. Similarly, determining whether and how circuits in the PBN become dysregulated may be important for understanding central pathways responsible for chronic pain.
We thank Sonja Bisch-Knaden for statistical advice, Mathias Ditzen for programming tools in IDL, ... more We thank Sonja Bisch-Knaden for statistical advice, Mathias Ditzen for programming tools in IDL, Walton Jones and Leslie B. Vosshall for help with generating UAS-Clomeleon flies, Thomas Kuner for helpful advice regarding Clomeleon imaging, Erich Buchner and Thomas Völler for assistance with the initial establishment of chloride imaging, Thomas Kuner, Andreas Schäfer and Marcus Stensmyr for thoughtful comments on the manuscript, and Michelle Wibraham and Andrew Davis for editorial assistance. S.S. generated transgenic Clomeleon flies and, together with A.F., established initial Clomeleon imaging experiments. V.G., A.R. M.S. and S.T. carried out imaging experiments. M.S.B. helped with data analysis. S.L.L. provided genetic expertise. B.S.H. provided intellectual and financial support. S.S. designed and supervised all experiments. V.G. and S.S. interpreted the results, prepared the figures, and, together with all other authors, wrote the paper.
Evaluating odor blends in sensory processing is a crucial step for signal recognition and executi... more Evaluating odor blends in sensory processing is a crucial step for signal recognition and execution of behavioral decisions. Using behavioral assays and 2-photon imaging, we have characterized the neural and behavioral correlates of mixture perception in the olfactory system of Drosophila. Mixtures of odors with opposing valences elicit strong inhibition in certain attractant-responsive input channels. This inhibition correlates with reduced behavioral attraction. We demonstrate that defined subsets of GABAergic interneurons provide the neuronal substrate of this computation at pre-and postsynaptic loci via GABA Band GABA A receptors, respectively. Intriguingly, manipulation of single input channels by silencing and optogenetic activation unveils a glomerulus-specific crosstalk between the attractant-and repellent-responsive circuits. This inhibitory interaction biases the behavioral output. Such a form of selective lateral inhibition represents a crucial neuronal mechanism in the processing of conflicting sensory information.
Although we have considerable knowledge about how odors are represented in the antennal lobe (AL)... more Although we have considerable knowledge about how odors are represented in the antennal lobe (AL), the insects' analogue to the olfactory bulb, we still do not fully understand how the different neurons in the AL network contribute to the olfactory code. In Drosophila melanogaster we can selectively manipulate specific neuronal populations to elucidate their function in odor processing. Here we silenced the synaptic transmission of two distinct subpopulations of multiglomerular GABAergic local interneurons (LN1 and LN2) using shibire (shi ts) and analyzed their impact on odor-induced glomerular activity at the AL input and output level. We verified that the employed shi ts construct effectively blocked synaptic transmission to the AL when expressed in olfactory sensory neurons. Notably, selective silencing of both LN populations did not significantly affect the odor-evoked activity patterns in the AL. Neither the glomerular input nor the glomerular output activity was modulated in comparison to the parental controls. We therefore conclude that these LN subpopulations, which cover one third of the total LN number, are not predominantly involved in odor identity coding per se. As suggested by their broad innervation patterns and contribution to long-term adaptation, they might contribute to AL-computation on a global and longer time scale. The survival of most animal species depends on processing of olfactory information from the environment. All animals are surrounded by an incredibly complex odor world comprised of pheromones, food or oviposition cues, as well as attractive or repellent odors that strongly affect behavioral decisions. How the olfactory system encodes the different chemical components to build an internal neural representation of the outer odor world still, remains an open question. A so far well-studied-but yet not fully understood-network model is the first olfactory neuropil of the insect brain, the antennal lobe (AL). The AL represents an analogous organization compared to the vertebrate olfactory bulb (for review cp. 1, 2). The morphological and functional subunits of the AL, the olfactory glomeruli, receive input via olfactory sensory neurons (OSN) located on the third antennal segment and on the maxillary palp 3. OSN activity is relayed to projection neurons (PNs) either through direct synaptic connections or via local interneurons (LNs). The PNs transmit AL activity via different neuronal tracts to higher-order processing centers 4. Different LN types shape the spatio-temporal response pattern of the glomeruli via a complex interplay of temporal excitation and inhibition 5-8. In honeybees this input-output computation results in a sharpening of responses in order to increase the contrast between different odor stimuli 5 , whereas in Drosophila melanogaster a broader odor tuning 9 and odor dependent modulation could be observed 10. However, both types of modulation result in an input-output transformation of the olfactory signal in the AL 9. The AL of Drosophila melanogaster comprises about 200 LNs connecting 54 glomeruli 11-13. The majority of LNs releases the inhibitory neurotransmitter gamma-amino-butyric-acid (GABA) 6, 14, 15 or glutamate 16 , but also
ZusammenfassungDuftstoffe geben Insekten überlebenswichtige Informationen über ihre Umwelt und st... more ZusammenfassungDuftstoffe geben Insekten überlebenswichtige Informationen über ihre Umwelt und steuern ihr Verhalten in vielfältiger Weise. Ein bemerkenswert empfindlicher und spezialisierter Geruchssinn ermöglicht es den Tieren dabei, auch noch geringste Mengen relevanter Duftstoffe zu registrieren und dadurch z. B. Nahrung, Artgenossen oder Feinde wahrzunehmen. In den letzten Jahren wurden erhebliche Fortschritte im Hinblick auf das Verständnis der molekularen Elemente und zellulären Vorgänge bei der Erkennung von Duftstoffen auf der Antenne, sowie den Prinzipien der Prozessierung von Duftsignalen im Gehirn erzielt. Die derzeitigen Befunde zeigen, dass „Riechhaare“ auf den Antennen chemosensorische Funktionseinheiten mit einer speziellen molekularen Ausstattung sind. Sie enthalten verschiedene Bindeproteine, die Duftstoffe zu spezifischen Rezeptoren in der dendritischen Membran der Riechsinneszellen transferieren. Die Bindung von Duftstoff an das Rezeptorprotein initiiert ionotrop...
Background: Egg-laying animals, such as insects, ensure the survival of their offspring by deposi... more Background: Egg-laying animals, such as insects, ensure the survival of their offspring by depositing their eggs in favorable environments. To identify suitable oviposition sites, insects, such as the vinegar fly Drosophila melanogaster, assess a complex range of features. The fly selectively lays eggs in fermenting fruit. However, the precise cues and conditions that trigger oviposition remain unclear, including whether flies are also selective for the fruit substrate itself. Results: Here, we demonstrate that flies prefer Citrus fruits as oviposition substrate. Flies detect terpenes characteristic of these fruits via a single class of olfactory sensory neurons, expressing odorant receptor Or19a. These neurons are necessary and sufficient for selective oviposition. In addition, we find that the Citrus preference is an ancestral trait, presumably representing an adaptation toward fruits found within the native African habitat. Moreover, we show that endoparasitoid wasps that parasitize fly larvae are strongly repelled by the smell of Citrus, as well as by valencene, the primary ligand of Or19a. Finally, larvae kept in substrates enriched with valencene suffer a reduced risk of parasitism. Conclusions: Our results demonstrate that a single dedicated olfactory pathway determines oviposition fruit substrate choice. Moreover, our work suggests that the fly's fruit preference-reflected in the functional properties of the identified neuron population-stem from a need to escape parasitism from endoparasitoid wasps.
Highlights d The neuronal composition of glomeruli is unique d Glomerular volume is determined la... more Highlights d The neuronal composition of glomeruli is unique d Glomerular volume is determined largely by the number of olfactory sensory neurons d Selectivity of a glomerulus is represented by the number of second-order neurons d Glomeruli encoding crucial odors possess a large number of PNs and low LN innervation
Uploads
Papers by Silke Sachse