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4108 Publications

Showing 1631-1640 of 4108 results
Svoboda Lab
03/13/08 | Genetic dissection of neural circuits.
Luo L, Callaway EM, Svoboda K
Neuron. 2008 Mar 13;57:634-60. doi: 10.1016/j.neuron.2008.01.002

Understanding the principles of information processing in neural circuits requires systematic characterization of the participating cell types and their connections, and the ability to measure and perturb their activity. Genetic approaches promise to bring experimental access to complex neural systems, including genetic stalwarts such as the fly and mouse, but also to nongenetic systems such as primates. Together with anatomical and physiological methods, cell-type-specific expression of protein markers and sensors and transducers will be critical to construct circuit diagrams and to measure the activity of genetically defined neurons. Inactivation and activation of genetically defined cell types will establish causal relationships between activity in specific groups of neurons, circuit function, and animal behavior. Genetic analysis thus promises to reveal the logic of the neural circuits in complex brains that guide behaviors. Here we review progress in the genetic analysis of neural circuits and discuss directions for future research and development.

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Svoboda Lab
04/18/18 | Genetic dissection of neural circuits: a decade of progress
Luo L, Callaway EM, Svoboda K
Neuron. 2018 Apr 18;98(2):256-81. doi: 10.1016/j.neuron.2018.03.040

Tremendous progress has been made since Neuron published our Primer on genetic dissection of neural circuits 10 years ago. Since then, cell-type-specific anatomical, neurophysiological, and perturbation studies have been carried out in a multitude of invertebrate and vertebrate organisms, linking neurons and circuits to behavioral functions. New methods allow systematic classification of cell types and provide genetic access to diverse neuronal types for studies of connectivity and neural coding during behavior. Here we evaluate key advances over the past decade and discuss future directions.

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04/01/08 | Genetic dissociation of ethanol sensitivity and memory formation in Drosophila melanogaster.
LaFerriere H, Guarnieri DJ, Sitaraman D, Diegelmann S, Heberlein U, Zars T
Genetics. 2008 Apr;178(4):1895-902. doi: 10.1534/genetics.107.084582

The ad hoc genetic correlation between ethanol sensitivity and learning mechanisms in Drosophila could overemphasize a common process supporting both behaviors. To challenge directly the hypothesis that these mechanisms are singular, we examined the learning phenotypes of 10 new strains. Five of these have increased ethanol sensitivity, and the other 5 do not. We tested place and olfactory memory in each of these lines and found two new learning mutations. In one case, altering the tribbles gene, flies have a significantly reduced place memory, elevated olfactory memory, and normal ethanol response. In the second case, mutation of a gene we name ethanol sensitive with low memory (elm), place memory was not altered, olfactory memory was sharply reduced, and sensitivity to ethanol was increased. In sum, however, we found no overall correlation between ethanol sensitivity and place memory in the 10 lines tested. Furthermore, there was a weak but nonsignificant correlation between ethanol sensitivity and olfactory learning. Thus, mutations that alter learning and sensitivity to ethanol can occur independently of each other and this implies that the set of genes important for both ethanol sensitivity and learning is likely a subset of the genes important for either process.

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Baker Lab
01/16/14 | Genetic identification and separation of innate and experience-dependent courtship behaviors in Drosophila.
Pan Y, Baker BS
Cell. 2014 Jan 16;156(1-2):236-48. doi: 10.1016/j.cell.2013.11.041

Wild-type D. melanogaster males innately possess the ability to perform a multistep courtship ritual to conspecific females. The potential for this behavior is specified by the male-specific products of the fruitless (fru(M)) gene; males without fru(M) do not court females when held in isolation. We show that such fru(M) null males acquire the potential for courtship when grouped with other flies; they apparently learn to court flies with which they were grouped, irrespective of sex or species and retain this behavior for at least a week. The male-specific product of the doublesex gene (dsx(M)) is necessary and sufficient for the acquisition of the potential for such experience-dependent courtship. These results reveal a process that builds, via dsx(M) and social experience, the potential for a more flexible sexual behavior, which could be evolutionarily conserved as dsx-related genes that function in sexual development are found throughout the animal kingdom.

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11/14/19 | Genetic Identification of Vagal Sensory Neurons That Control Feeding
Ling Bai , Sheyda Mesgarzadeh , Karthik S. Ramesh , Erica L. Huey , Yin Liu , Lindsay A. Gray , Tara J. Aitken , Yiming Chen , Lisa R. Beutler , Jamie S. Ahn , Linda Madisen , Hongkui Zeng , Mark A. Krasnow , Zachary A. Knight
Cell. 11/2019;179:1129-1143.e23. doi: https://doi.org/10.1016/j.cell.2019.10.031

Summary Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here, we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.

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Simpson Lab
10/20/11 | Genetic manipulation of genes and cells in the nervous system of the fruit fly.
Venken KJ, Simpson JH, Bellen HJ
Neuron. 2011 Oct 20;72(2):202-30. doi: 10.1016/j.neuron.2011.09.021

Research in the fruit fly Drosophila melanogaster has led to insights in neural development, axon guidance, ion channel function, synaptic transmission, learning and memory, diurnal rhythmicity, and neural disease that have had broad implications for neuroscience. Drosophila is currently the eukaryotic model organism that permits the most sophisticated in vivo manipulations to address the function of neurons and neuronally expressed genes. Here, we summarize many of the techniques that help assess the role of specific neurons by labeling, removing, or altering their activity. We also survey genetic manipulations to identify and characterize neural genes by mutation, overexpression, and protein labeling. Here, we attempt to acquaint the reader with available options and contexts to apply these methods.

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04/01/05 | Genetic mapping of aphicarus -- a sex-linked locus controlling a wing polymorphism in the pea aphid (Acyrthosiphon pisum).
Braendle C, Caillaud MC, Stern DL
Heredity (Edinb). 2005 Apr;94(4):435-42. doi: 10.1038/sj.hdy.6800633

We have initiated research to determine the genetic basis of a male wing polymorphism in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphididae). Previous studies showed that this polymorphism is controlled by a single biallelic locus, which we name aphicarus (api), on the X chromosome. Our objectives were to confirm that api segregates as a polymorphism of a single gene on the X chromosome, and to obtain molecular markers flanking api that can be used as a starting point for high-resolution genetic and physical mapping of the target region, which will ultimately allow the cloning of api. We have established an F2 population segregating for api and have generated X-linked AFLP markers. The segregation pattern of api in the F2 population shows that the male wing polymorphism segregates as a polymorphism of a single gene, or set of closely linked genes on the X chromosome. Using a subset of 78 F2 males, we have constructed a linkage map of the chromosomal region encompassing api using seven AFLP markers. The map spans 74.1 cM and we have mapped api to an interval of 10 cM. In addition, we confirmed X linkage of our AFLP markers and api by using one X-linked marker developed in an earlier study. Our study presents the first mapping of a gene with known function in aphids, and the results indicate that target gene mapping in aphids is feasible.

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05/01/06 | Genetic mosaic with dual binary transcriptional systems in Drosophila.
Lai S, Lee T
Nature Neuroscience. 2006 May;9(5):703-9. doi: 10.1038/nn1681

MARCM (mosaic analysis with a repressible cell marker) involves specific labeling of GAL80-minus and GAL4-positive homozygous cells in otherwise heterozygous tissues. Here we demonstrate how the concurrent use of two independent binary transcriptional systems may facilitate complex MARCM studies in the Drosophila nervous system. By fusing LexA with the VP16 acidic activation domain (VP16) or the GAL4 activation domain (GAD), we obtained both GAL80-insensitive and GAL80-suppressible transcriptional factors. LexA::VP16 can mediate MARCM-independent binary transgene induction in mosaic organisms. The incorporation of LexA::GAD into MARCM, which we call dual-expression-control MARCM, permits the induction of distinct transgenes in different patterns among GAL80-minus cells in mosaic tissues. Lineage analysis with dual-expression-control MARCM suggested the presence of neuroglioblasts in the developing optic lobes but did not indicate the production of glia by postembryonic mushroom body neuronal precursors. In addition, dual-expression-control MARCM with a ubiquitous LexA::GAD driver revealed many unidentified cells in the GAL4-GH146-positive projection neuron lineages.

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03/13/18 | Genetic reagents for making split-GAL4 lines in Drosophila.
Dionne H, Hibbard KL, Cavallaro A, Kao J, Rubin GM
Genetics . 2018 March;209(1):31-5. doi: 10.1101/197509

The ability to reproducibly target expression of transgenes to small, defined subsets of cells is a key experimental tool for understanding many biological processes. The Drosophila nervous system contains thousands of distinct cell types and it has generally not been possible to limit expression to one or a few cell types when using a single segment of genomic DNA as an enhancer to drive expression. Intersectional methods, in which expression of the transgene only occurs where two different enhancers overlap in their expression patterns, can be used to achieve the desired specificity. This report describes a set of over 2,800 transgenic lines for use with the split-GAL4 intersectional method.

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Zlatic Lab

Drosophila sensory neurons form distinctive terminal branch patterns in the developing neuropile of the embryonic central nervous system. In this paper we make a genetic analysis of factors regulating arbor position. We show that mediolateral position is determined in a binary fashion by expression (chordotonal neurons) or nonexpression (multidendritic neurons) of the Robo3 receptor for the midline repellent Slit. Robo3 expression is one of a suite of chordotonal neuron properties that depend on expression of the proneural gene atonal. Different features of terminal branches are separately regulated: an arbor can be shifted mediolaterally without affecting its dorsoventral location, and the distinctive remodeling of one arbor continues as normal despite this arbor shifting to an abnormal position in the neuropile.

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