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  1. Article ; Online: A system for the high-throughput analysis of acute thermal avoidance and adaptation in

    Lia, Andrei-Stefan / Glauser, Dominique A

    Journal of biological methods

    2020  Volume 7, Issue 1, Page(s) e129

    Abstract: Nociception and its plasticity are essential biological processes controlling adaptive behavioral responses in animals. These processes are also linked to different pain conditions in human and have received considerable attention, ... ...

    Abstract Nociception and its plasticity are essential biological processes controlling adaptive behavioral responses in animals. These processes are also linked to different pain conditions in human and have received considerable attention, notably
    Language English
    Publishing date 2020-03-17
    Publishing country United States
    Document type Journal Article
    ISSN 2326-9901
    ISSN (online) 2326-9901
    DOI 10.14440/jbm.2020.324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Specific Ion Channels Control Sensory Gain, Sensitivity, and Kinetics in a Tonic Thermonociceptor.

    Saro, Gabriella / Lia, Andrei-Stefan / Thapliyal, Saurabh / Marques, Filipe / Busch, Karl Emanuel / Glauser, Dominique A

    Cell reports

    2020  Volume 30, Issue 2, Page(s) 397–408.e4

    Abstract: Pain sensation and aversive behaviors entail the activation of nociceptor neurons, whose function is largely conserved across animals. The functional heterogeneity of nociceptors and ethical concerns are challenges for their study in mammalian models. ... ...

    Abstract Pain sensation and aversive behaviors entail the activation of nociceptor neurons, whose function is largely conserved across animals. The functional heterogeneity of nociceptors and ethical concerns are challenges for their study in mammalian models. Here, we investigate the function of a single type of genetically identified C. elegans thermonociceptor named FLP. Using calcium imaging in vivo, we demonstrate that FLP encodes thermal information in a tonic and graded manner over a wide thermal range spanning from noxious cold to noxious heat (8°C-36°C). This tonic-signaling mode allows FLP to trigger sustained behavioral changes necessary for escape behavior. Furthermore, we identify specific transient receptor potential, voltage-gated calcium, and sodium "leak" channels controlling sensory gain, thermal sensitivity, and signal kinetics, respectively, and show that the ryanodine receptor is required for long-lasting activation. Our work elucidates the task distribution among specific ion channels to achieve remarkable sensory properties in a tonic thermonociceptor in vivo.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Caenorhabditis elegans ; Ion Channels/metabolism ; Nociceptors/metabolism ; Optogenetics/methods ; Temperature ; Thermosensing/physiology
    Chemical Substances Ion Channels
    Language English
    Publishing date 2020-01-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2019.12.029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Identification of avoidance genes through neural pathway-specific forward optogenetics.

    Marques, Filipe / Saro, Gabriella / Lia, Andrei-Stefan / Poole, Richard J / Falquet, Laurent / Glauser, Dominique A

    PLoS genetics

    2019  Volume 15, Issue 12, Page(s) e1008509

    Abstract: Understanding how the nervous system bridges sensation and behavior requires the elucidation of complex neural and molecular networks. Forward genetic approaches, such as screens conducted in C. elegans, have successfully identified genes required to ... ...

    Abstract Understanding how the nervous system bridges sensation and behavior requires the elucidation of complex neural and molecular networks. Forward genetic approaches, such as screens conducted in C. elegans, have successfully identified genes required to process natural sensory stimuli. However, functional redundancy within the underlying neural circuits, which are often organized with multiple parallel neural pathways, limits our ability to identify 'neural pathway-specific genes', i.e. genes that are essential for the function of some, but not all of these redundant neural pathways. To overcome this limitation, we developed a 'forward optogenetics' screening strategy in which natural stimuli are initially replaced by the selective optogenetic activation of a specific neural pathway. We used this strategy to address the function of the polymodal FLP nociceptors mediating avoidance of noxious thermal and mechanical stimuli. According to our expectations, we identified both mutations in 'general' avoidance genes that broadly impact avoidance responses to a variety of natural noxious stimuli (unc-4, unc-83, and eat-4) and mutations that produce a narrower impact, more restricted to the FLP pathway (syd-2, unc-14 and unc-68). Through a detailed follow-up analysis, we further showed that the Ryanodine receptor UNC-68 acts cell-autonomously in FLP to adjust heat-evoked calcium signals and aversive behaviors. As a whole, our work (i) reveals the importance of properly regulated ER calcium release for FLP function, (ii) provides new entry points for new nociception research and (iii) demonstrates the utility of our forward optogenetic strategy, which can easily be transposed to analyze other neural pathways.
    MeSH term(s) Animals ; Avoidance Learning ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/physiology ; Caenorhabditis elegans Proteins/genetics ; Calcium Signaling ; Cytoskeletal Proteins/genetics ; Gene Expression Regulation ; Homeodomain Proteins/genetics ; Intercellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/genetics ; Nuclear Proteins/genetics ; Optogenetics/methods ; Receptors, Glutamate/genetics ; Ryanodine Receptor Calcium Release Channel/genetics
    Chemical Substances Caenorhabditis elegans Proteins ; Cytoskeletal Proteins ; Eat-4 protein, C elegans ; Homeodomain Proteins ; Intercellular Signaling Peptides and Proteins ; Membrane Proteins ; Nuclear Proteins ; Receptors, Glutamate ; Ryanodine Receptor Calcium Release Channel ; SYD-2 protein, C elegans ; UNC-14 protein, C elegans ; Unc-68 protein, C elegans ; Unc-83 protein, C elegans ; unc-4 protein, C elegans (146210-10-8)
    Language English
    Publishing date 2019-12-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1008509
    Database MEDical Literature Analysis and Retrieval System OnLINE

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