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In JoVE (1)
Other Publications (10)
Articles by Matthieu Louis in JoVE
High-resolution Measurement of Odor-Driven Behavior in Drosophila Larvae
Matthieu Louis, Silvia Piccinotti, Leslie B. Vosshall
Laboratory of Neurogenetics and Behavior, Rockefeller University
In this video article, we describe a new method allowing the construction of odorant gradients with stable and controllable geometries. We briefly illustrate how these gradients can be used to screen for olfactory defects (full and partial anosmia) and to study more subtle features of chemotaxis behavior.
Other articles by Matthieu Louis on PubMed
Science's STKE : Signal Transduction Knowledge Environment. Jul, 2002 | Pubmed ID: 12149512
Although gene expression can be regulated in a graded or a binary fashion, the majority of eukaryotic genes are either fully activated or not expressed at all in individual cells. This binary response might be an inherent property of many eukaryotic promoters. Analysis of transcription under the control of yeast GAL1 promoter suggests, however, that graded and binary modes of transcription are not mutually exclusive, but that both can occur at the same promoter when the activity of different signaling pathways is varied. In view of that, it can be expected that forthcoming experimental studies on the combinatorial effects of signaling and transcriptional mechanisms will reveal new strategies for generating graded or binary responses.
A Theoretical Model for the Regulation of Sex-lethal, a Gene That Controls Sex Determination and Dosage Compensation in Drosophila Melanogaster
Genetics. Nov, 2003 | Pubmed ID: 14668388
Cell fate commitment relies upon making a choice between different developmental pathways and subsequently remembering that choice. Experimental studies have thoroughly investigated this central theme in biology for sex determination. In the somatic cells of Drosophila melanogaster, Sex-lethal (Sxl) is the master regulatory gene that specifies sexual identity. We have developed a theoretical model for the initial sex-specific regulation of Sxl expression. The model is based on the well-documented molecular details of the system and uses a stochastic formulation of transcription. Numerical simulations allow quantitative assessment of the role of different regulatory mechanisms in achieving a robust switch. We establish on a formal basis that the autoregulatory loop involved in the alternative splicing of Sxl primary transcripts generates an all-or-none bistable behavior and constitutes an efficient stabilization and memorization device. The model indicates that production of a small amount of early Sxl proteins leaves the autoregulatory loop in its off state. Numerical simulations of mutant genotypes enable us to reproduce and explain the phenotypic effects of perturbations induced in the dosage of genes whose products participate in the early Sxl promoter activation.
Current Biology : CB. Dec, 2005 | Pubmed ID: 16332533
Odorant receptors (ORs) are thought to act in a combinatorial fashion, in which odor identity is encoded by the activation of a subset of ORs and the olfactory sensory neurons (OSNs) that express them. The extent to which a single OR contributes to chemotaxis behavior is not known. We investigated this question in Drosophila larvae, which represent a powerful genetic system to analyze the contribution of individual OSNs to odor coding.
Nature Neuroscience. Feb, 2008 | Pubmed ID: 18157126
Neural comparisons of bilateral sensory inputs are essential for visual depth perception and accurate localization of sounds in space. All animals, from single-cell prokaryotes to humans, orient themselves in response to environmental chemical stimuli, but the contribution of spatial integration of neural activity in olfaction remains unclear. We investigated this problem in Drosophila melanogaster larvae. Using high-resolution behavioral analysis, we studied the chemotaxis behavior of larvae with a single functional olfactory neuron on either the left or right side of the head, allowing us to examine unilateral or bilateral olfactory input. We developed new spectroscopic methods to create stable odorant gradients in which odor concentrations were experimentally measured. In these controlled environments, we observed that a single functional neuron provided sufficient information to permit larval chemotaxis. We found additional evidence that the overall accuracy of navigation is enhanced by the increase in the signal-to-noise ratio conferred by bilateral sensory input.
Journal of Molecular Biology. Dec, 2008 | Pubmed ID: 18938177
Protein sequestration occurs when an active protein is sequestered by a repressor into an inactive complex. Using mathematical and computational modeling, we show how this regulatory mechanism (called "molecular titration") can generate ultrasensitive or "all-or-none" responses that are equivalent to highly cooperative processes. The ultrasensitive nature of the input-output response is mainly determined by two parameters: the dimer dissociation constant and the repressor concentration. Because in vivo concentrations are tunable through a variety of mechanisms, molecular titration represents a flexible mechanism for generating ultrasensitivity. Using physiological parameters, we report how details of in vivo protein degradation affect the strength of the ultrasensitivity at steady state. Given that developmental systems often transduce signals into cell-fate decisions on timescales incompatible with steady state, we further examine whether molecular titration can produce ultrasensitive responses within physiologically relevant time intervals. Using Drosophila somatic sex determination as a developmental paradigm, we demonstrate that molecular titration can generate ultrasensitivity on timescales compatible with most cell-fate decisions. Gene duplication followed by loss-of-function mutations can create dominant negatives that titrate and compete with the original protein. Dominant negatives are abundant in gene regulatory circuits, and our results suggest that molecular titration might be generating an ultrasensitive response in these networks.
Journal of Biology. 2009 | Pubmed ID: 19171076
Most odors are perceived to have the same quality over a large concentration range, but the neural mechanisms that permit concentration-invariant olfactory perception are unknown. In larvae of the vinegar fly Drosophila melanogaster, odors are sensed by an array of 25 odorant receptors expressed in 21 olfactory sensory neurons (OSNs). We investigated how subsets of larval OSNs with overlapping but distinct response properties cooperate to mediate perception of a given odorant across a range of concentrations.
Journal of Neurogenetics. Sep, 2010 | Pubmed ID: 20807100
Learnt predictive behavior faces a dilemma: predictive stimuli will never 'replay' exactly as during the learning event, requiring generalization. In turn, minute differences can become meaningful, prompting discrimination. To provide a study case for an adaptive adjustment of this generalization-discrimination balance, the authors ask whether Drosophila melanogaster larvae are able to either generalize or discriminate between two odors (1-octen-3-ol and 3-octanol), depending on the task. The authors find that after discriminatively rewarding one but not the other odor, larvae show conditioned preference for the rewarded odor. On the other hand, no odor specificity is observed after nondiscriminative training, even if the test involves a choice between both odors. Thus, for this odor pair at least, discrimination training is required to confer an odor-specific memory trace. This requires that there is at least some difference in processing between the two odors already at the beginning of the training. Therefore, as a default, there is a small yet salient difference in processing between 1-octen-3-ol and 3-octanol; this difference is ignored after nondiscriminative training (generalization), whereas it is accentuated by odor-specific reinforcement (discrimination). Given that, as the authors show, both faculties are lost in anosmic Or83b(1) mutants, this indicates an adaptive adjustment of the generalization-discrimination balance in larval Drosophila, taking place downstream of Or83b-expressing sensory neurons.
Frontiers in Cellular Neuroscience. 2010 | Pubmed ID: 20407585
Early in evolution, the ability to sense and respond to changing environments must have provided a critical survival advantage to living organisms. From bacteria and worms to flies and vertebrates, sophisticated mechanisms have evolved to enhance odor detection and localization. Here, we review several modes of chemotaxis. We further consider the relevance of a striking and recurrent motif in the organization of invertebrate and vertebrate sensory systems, namely the existence of two symmetrical olfactory sensors. By combining our current knowledge about the olfactory circuits of larval and adult Drosophila, we examine the molecular and neural mechanisms underlying robust olfactory perception and extend these analyses to recent behavioral studies addressing the relevance and function of bilateral olfactory input for gradient detection. Finally, using a comparative theoretical approach based on Braitenberg's vehicles, we speculate about the relationships between anatomy, circuit architecture and stereotypical orientation behaviors.
Nature Communications. 2011 | Pubmed ID: 21863008
The ability to respond to chemical stimuli is fundamental to the survival of motile organisms, but the strategies underlying odour tracking remain poorly understood. Here we show that chemotaxis in Drosophila melanogaster larvae is an active sampling process analogous to sniffing in vertebrates. Combining computer-vision algorithms with reconstructed olfactory environments, we establish that larvae orient in odour gradients through a sequential organization of stereotypical behaviours, including runs, stops, lateral head casts and directed turns. Negative gradients, integrated during runs, control the timing of turns. Positive gradients detected through high-amplitude head casts determine the direction of individual turns. By genetically manipulating the peripheral olfactory circuit, we examine how orientation adapts to losses and gains of function in olfactory input. Our findings suggest that larval chemotaxis represents an intermediate navigation strategy between the biased random walks of Escherichia Coli and the stereo-olfaction observed in rats and humans.
Current Opinion in Neurobiology. Dec, 2011 | Pubmed ID: 22169055
The fruit fly Drosophila larva demonstrates a sophisticated repertoire of behavior under the control of a numerically simple neural system. Historically, the stereotyped responses of larvae to light and odors captivated the attention of biologists. More recently, the sensory receptors responsible for chemosensation, thermosensation, and vision have been identified. While our understanding of the molecular logic of perception has clearly progressed, little is known about the neural and computational mechanisms guiding movement in sensory gradients. Here we review evidence that larvae orient based on active sensation-a feature distinct from the strategies used by simpler model organisms. Reorientation maneuvers are controlled by the spatiotemporal integration of changes in stimulus intensity detected during runs and lateral head movements.