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Inhibitory circuits control leg movements during Drosophila grooming.

Durafshan Sakeena Syed | Primoz Ravbar | Julie H Simpson
eLife | 2026

Limbs execute diverse actions coordinated by the nervous system through multiple motor programs. The basic architecture of motor neurons that activate muscles which articulate joints for antagonistic flexion and extension movements is conserved from flies to vertebrates. While excitatory premotor circuits are expected to establish sets of leg motor neurons that work together, our study uncovered an instructive role for inhibitory circuits - including their ability to generate rhythmic leg movements. Using electron microscopy data in the Drosophila nerve cord, we categorized ~120 GABAergic inhibitory neurons from the 13 A and 13B hemilineages into classes based on similarities in morphology and connectivity. By mapping their connections, we uncovered pathways for inhibiting specific groups of motor neurons, disinhibiting antagonistic counterparts, and inducing alternation between flexion and extension. We tested the function of specific inhibitory neurons through optogenetic activation and silencing, using high-resolution quantitative analysis of leg movements during grooming. We combined findings from anatomical and behavioral analyses to construct a computational model that can reproduce major aspects of the observed behavior, demonstrating that these premotor inhibitory circuits can generate rhythmic leg movements.

Pubmed ID: 41591902

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: RF1 NS132900
  • Agency: NIH HHS, United States
    Id: NS132900
  • Agency: National Science Foundation,
    Id: NSF1943276

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This is a list of tools and resources that we have found mentioned in this publication.


National Institutes of Health (tool)

RRID:SCR_011417

NIH is the nations medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research. Helping to lead the way toward important medical discoveries that improve peoples health and save lives, NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. NIH research impacts: * child and teen health, * men's health, * minority health, * seniors' health, * women's health, and * wellness and lifestyle issues. Composed of 27 Institutes and Centers, the NIH provides leadership and financial support to researchers in every state and throughout the world.

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National Science Foundation (tool)

RRID:SCR_012938

An independent federal agency created by Congress to promote the progress of science; to advance the national health, prosperity, and welfare; to secure the national defense They are the funding source for approximately 20 percent of all federally supported basic research conducted by America''s colleges and universities. In many fields such as mathematics, computer science and the social sciences, NSF is the major source of federal backing. NSF leadership has two major components: a director who oversees NSF staff and management responsible for program creation and administration, merit review, planning, budget and day-to-day operations; and a 24-member National Science Board (NSB) of eminent individuals that meets six times a year to establish the overall policies of the foundation.The director and all Board members serve six year terms. Each of them, as well as the NSF deputy director, is appointed by the President of the United States and confirmed by the U.S. Senate. At present, NSF has a total workforce of about 2,100 at its Arlington, Va., headquarters, including approximately 1,400 career employees, 200 scientists from research institutions on temporary duty, 450 contract workers and the staff of the NSB office and the Office of the Inspector General. NSF is the only federal agency whose mission includes support for all fields of fundamental science and engineering, except for medical sciences. They are tasked with keeping the United States at the leading edge of discovery in areas from astronomy to geology to zoology. So, in addition to funding research in the traditional academic areas, the agency also supports high-risk, high pay-off ideas, novel collaborations and numerous projects that may seem like science fiction today, but which the public will take for granted tomorrow. And in every case, they ensure that research is fully integrated with education so that today''s revolutionary work will also be training tomorrow''s top scientists and engineers NSF''s task of identifying and funding work at the frontiers of science and engineering is not a top-down process.

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HA-Tag (C29F4) Rabbit mAb (antibody)

RRID:AB_1549585

This monoclonal targets HA-Tag

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DYKDDDDK Epitope Tag Antibody (antibody)

RRID:AB_1625982

This monoclonal targets DYKDDDDK Epitope Tag

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Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

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Mouse anti V5-Tag:DyLight®550 (antibody)

RRID:AB_2687576

This monoclonal targets V5-Tag

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Adobe Photoshop (software resource)

RRID:SCR_014199

Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.

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MATLAB (software resource)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

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Adobe Illustrator (software resource)

RRID:SCR_010279

Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.

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CATMAID (software resource)

RRID:SCR_006278

A toolkit designed to navigate, share and collaboratively annotate massive image data sets of biological specimens. The interface enables synchronized navigation through multiple registered datasets even at vastly different scales such as in comparisons between optical and electron microscopy. The interface is inspired by GoogleMaps, with which it shares basic navigation concepts, enhanced to allow the exploration of 3D biological image data acquired by optical or physical sectioning microscopy techniques. The interface enables seamless sharing of regions of interest through bookmarks and synchronized navigation through multiple registered data sets. With massive biological image data sets it is unrealistic to create a sustainable centralized repository. A unique feature of CATMAID is its partially decentralized architecture where the presented image data can reside on any Internet accessible server and yet can be easily cross-referenced in the central database. In this way no image data are duplicated and the data producers retain full control over their images. CATMAID is intended to serve as data sharing platform for biologists using high-resolution imaging techniques to probe large specimens. Any high-throughput, high-content imaging project such as gene expression pattern screens would benefit from the interface for data sharing and annotation. Features: * Fast terabyte-scale image data browsing * Collaborative microcircuit reconstruction and annotation * Flexible hierarchical semantic annotation * Multiple linked image stack display * Neuron Catalog * SVG and WebGL-based neuronal morphology viewer * Open source software

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w[*]; P{y[+t7.7] w[+mC]=20XUAS-IVS-mCD8::GFP}attP2 (organism)

RRID:BDSC_32194

Drosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=20XUAS-IVS-mCD8::GFP}attP2 from BDSC.

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w[1118]; P{y[+t7.7] w[+mC]=p65.AD.Uw}attP40; P{y[+t7.7] w[+mC]=GAL4.DBD.Uw}attP2 (organism)

RRID:BDSC_79603

Drosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=p65.AD.Uw}attP40; P{y[+t7.7] w[+mC]=GAL4.DBD.Uw}attP2 from BDSC.

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w[1118] P{y[+t7.7] w[+mC]=10xUAS-IVS-myr::smGdP-HA}attP18 P{y[+t7.7] w[+mC]=13xLexAop2-IVS-myr::smGdP-V5}su(Hw)attP8; sna[Sco]/CyO; P{y[+t7.7] w[+mC]=R35G04-GAL4.DBD}attP2 (organism)

RRID:BDSC_70351

Drosophila melanogaster with name w[1118] P{y[+t7.7] w[+mC]=10xUAS-IVS-myr::smGdP-HA}attP18 P{y[+t7.7] w[+mC]=13xLexAop2-IVS-myr::smGdP-V5}su(Hw)attP8; sna[Sco]/CyO; P{y[+t7.7] w[+mC]=R35G04-GAL4.DBD}attP2 from BDSC.

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w[1118]; P{y[+t7.7] w[+mC]=20XUAS-IVS-CsChrimson.mVenus}attP40 (organism)

RRID:BDSC_55135

Drosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=20XUAS-IVS-CsChrimson.mVenus}attP40 from BDSC.

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Python Programming Language (software resource)

RRID:SCR_008394

Programming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.

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RRID:BDSC_64087

Drosophila melanogaster with name w[1118] P{y[+t7.7] w[+mC]=R57C10-FLPL}su(Hw)attP8; PBac{y[+mDint2] w[+mC]=10xUAS(FRT.stop)myr::smGdP-HA}VK00005 P{y[+t7.7] w[+mC]=10xUAS(FRT.stop)myr::smGdP-V5-THS-10xUAS(FRT.stop)myr::smGdP-FLAG}su(Hw)attP1 from BDSC.

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DeepLabCut (software resource)

RRID:SCR_021391

Open source software package for markerless pose estimation. 2D keypoint detection in animals.

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w[*]; P{y[+t7.7] w[+mC]=UAS-GtACR1.d.EYFP}attP2 (organism)

RRID:BDSC_92983

Drosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=UAS-GtACR1.d.EYFP}attP2 from BDSC.

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w[1118]; P{y[+t7.7] w[+mC]=R11C07-p65.AD}attP40; MKRS/TM6B, Tb[1] (organism)

RRID:BDSC_70533

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RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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RRID:SCR_000432

Open source and enterprise ready professional software for R statistical computing environment. Integrated development environment for R. Includes console, syntax highlighting editor that supports direct code execution, as well as tools for plotting, history, debugging and workspace management. Available in open source and commercial editions and runs on desktop Windows, Mac, and Linux or in browser connected to RStudio Server or RStudio Server Pro (Debian/Ubuntu, RedHat/CentOS, and SUSE Linux).

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Neuroglancer (software resource)

RRID:SCR_015631

WebGL-based viewer for volumetric data. It is capable of displaying arbitrary (non axis-aligned) cross-sectional views of volumetric data, as well as 3-D meshes and line-segment based models (skeletons).

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