Publications by authors named "Scott Kreher"

6 Publications

  • Page 1 of 1

Complex and non-redundant signals from individual odor receptors that underlie chemotaxis behavior in Drosophila melanogaster larvae.

Biol Open 2014 Sep 19;3(10):947-57. Epub 2014 Sep 19.

Department of Biological Sciences, Dominican University, 7900 West Division Street, Parmer Hall 244, River Forest, IL 60305, USA

The rules by which odor receptors encode odors and allow behavior are still largely unexplored. Although large data sets of electrophysiological responses of receptors to odors have been generated, few hypotheses have been tested with behavioral assays. We use a data set on odor responses of Drosophila larval odor receptors coupled with chemotaxis behavioral assays to examine rules of odor coding. Using mutants of odor receptors, we have found that odor receptors with similar electrophysiological responses to odors across concentrations play non-redundant roles in odor coding at specific odor concentrations. We have also found that high affinity receptors for odors determine behavioral response thresholds, but the rules for determining peak behavioral responses are more complex. While receptor mutants typically show loss of attraction to odors, some receptor mutants result in increased attraction at specific odor concentrations. The odor receptor mutants were rescued using transgenic expression of odor receptors, validating assignment of phenotypes to the alleles. Vapor pressures alone cannot fully explain behavior in our assay. Finally, some odors that did not elicit strong electrophysiological responses are associated with behavioral phenotypes upon examination of odor receptor mutants. This result is consistent with the role of sensory neurons in lateral inhibition via local interneurons in the antennal lobe. Taken together, our results suggest a complexity of odor coding rules even in a simple olfactory sensory system.
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http://dx.doi.org/10.1242/bio.20148573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197443PMC
September 2014

Translation of sensory input into behavioral output via an olfactory system.

Neuron 2008 Jul;59(1):110-24

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.

We investigate the logic by which sensory input is translated into behavioral output. First we provide a functional analysis of the entire odor receptor repertoire of an olfactory system. We construct tuning curves for the 21 functional odor receptors of the Drosophila larva and show that they sharpen at lower odor doses. We construct a 21-dimensional odor space from the responses of the receptors and find that the distance between two odors correlates with the extent to which one odor masks the other. Mutational analysis shows that different receptors mediate the responses to different concentrations of an odorant. The summed response of the entire receptor repertoire correlates with the strength of the behavioral response. The activity of a small number of receptors is a surprisingly powerful predictor of behavior. Odors that inhibit more receptors are more likely to be repellents. Odor space is largely conserved between two dissimilar olfactory systems.
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http://dx.doi.org/10.1016/j.neuron.2008.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2496968PMC
July 2008

Membrane topology of the Drosophila OR83b odorant receptor.

FEBS Lett 2007 Dec 20;581(29):5601-4. Epub 2007 Nov 20.

Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Svante Arrheniusv 12, SE-106 91, Stockholm, Sweden.

By analogy to mammals, odorant receptors (ORs) in insects, such as Drosophila melanogaster, have long been thought to belong to the G-protein coupled receptor (GPCR) superfamily. However, recent work has cast doubt on this assumption and has tentatively suggested an inverted topology compared to the canonical N(out) - C(in) 7 transmembrane (TM) GPCR topology, at least for some Drosophila ORs. Here, we report a detailed topology mapping of the Drosophila OR83b receptor using engineered glycosylation sites as topology markers. Our results are inconsistent with a classical GPCR topology and show that OR83b has an intracellular N-terminus, an extracellular C-terminus, and 7TM helices.
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http://dx.doi.org/10.1016/j.febslet.2007.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176074PMC
December 2007

The molecular basis of odor coding in the Drosophila larva.

Neuron 2005 May;46(3):445-56

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.

We have analyzed the molecular basis of odor coding in the Drosophila larva. A subset of Or genes is found to be expressed in larval olfactory receptor neurons (ORNs). Using an in vivo expression system and electrophysiology, we demonstrate that these genes encode functional odor receptors and determine their response spectra with 27 odors. The receptors vary in their breadth of tuning, exhibit both excitation and inhibition, and show different onset and termination kinetics. An individual receptor appears to transmit signals via a single ORN to a single glomerulus in the larval antennal lobe. We provide a spatial map of odor information in the larval brain and find that ORNs with related functional specificity map to related spatial positions. The results show how one family of receptors underlies odor coding in two markedly different olfactory systems; they also provide a molecular mechanism to explain longstanding observations of larval odor discrimination.
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http://dx.doi.org/10.1016/j.neuron.2005.04.007DOI Listing
May 2005

An optimized CD8+ T-cell response controls productive and latent gammaherpesvirus infection.

J Virol 2005 Feb;79(4):2573-83

Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, Box 8118, St. Louis, MO 63110, USA.

Strategies to prime CD8(+) T cells against Murine gammaherpesvirus 68 (gammaHV68; MHV68) latency have, to date, resulted in only limited effects. While early forms of latency (<21 days) were significantly reduced, effects were not seen at later times, indicating loss of control by the primed CD8(+) T cells. In the present study, we evaluated CD8(+) T cells in an optimized system, consisting of OTI T-cell-receptor (TCR) transgenic mice, which generate clonal CD8(+) T cells specific for K(b)-SIINFEKL of OVA, and a recombinant gammaHV68 that expresses OVA (gammaHV68.OVA). Our aim was to test whether this optimized system would result in more effective control not only of acute infection but also of later forms of latent infection than was seen with previous strategies. First, we show that OTI CD8(+) T cells effectively controlled acute replication of gammaHV68.OVA in liver, lung, and spleen at 8 and 16 days after infection of OTI/RAG mice, which lack expression of B and CD4(+) T cells. However, we found that, despite eliminating detectable acute replication, the OTI CD8(+) T cells did not prevent the establishment of latency in the OTI/RAG mice. We next evaluated the effectiveness of OTI T cells in OTI/B6 animals, which express B cells--a major site of latency in wild-type mice--and CD4(+) T cells. In OTI/B6 mice OTI CD8(+) T cells not only reduced the frequency of cells that reactivate from latency and the frequency of cells bearing the viral genome at 16 days after infection (similar to what has been reported before) but also were effective at reducing latency at 42 days after infection. Together, these data show that CD8(+) T cells are sufficient, in the absence of B cells and CD4(+) T cells, for effective control of acute replication. The data also demonstrate for the first time that a strong CD8(+) T-cell response can limit long-term latent infection.
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http://dx.doi.org/10.1128/JVI.79.4.2573-2583.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC546552PMC
February 2005

An optimized CD4 T-cell response can control productive and latent gammaherpesvirus infection.

J Virol 2004 Jul;78(13):6827-35

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

CD4 T cells are important for control of infection with murine gammaherpesvirus 68 (gamma HV68), but it is not known whether CD4 T cells function via provision of help to other lymphocyte subsets, such as B cells and CD8 T cells, or have an independent antiviral function. Moreover, under conditions of natural infection, the CD4 T-cell response is not sufficient to eliminate infection. To determine the functional capacities of CD4 T cells under optimal or near-optimal conditions and to determine whether CD4 T cells can control gamma HV68 infection in the absence of CD8 T cells or B cells, we studied the effect of ovalbumin (OVA)-specific CD4 T cells on infection with a recombinant gamma HV68 that expresses OVA. OVA-specific CD4 T cells limited acute gamma HV68 replication and prolonged the life of infected T-cell receptor-transgenic RAG (DO.11.10/RAG) mice, demonstrating CD4 T-cell antiviral activity, independent of CD8 T cells and B cells. Despite CD4 T-cell-mediated control of acute infection, latent infection was established in DO.11.10/RAG mice. However, OVA-specific CD4 T cells reduced the frequency of latently infected cells both early (16 days postinfection) and late (42 days postinfection) after infection of mice containing CD8 T cells and B cells (DO.11.10 mice). These results show that OVA-specific CD4 T cells have B-cell and CD8 T-cell-independent antiviral functions in the control of acute infection and can, in the absence of preexisting CD8 T-cell or B-cell immunity, inhibit the establishment of gammaherpesvirus latency.
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http://dx.doi.org/10.1128/JVI.78.13.6827-6835.2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC421646PMC
July 2004