GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely moving Drosophila
Walking is a complex rhythmic locomotor behavior generated by sequential and periodical contraction of muscles essential for coordinated control of movements of legs and leg joints. Studies of walking in vertebrates and invertebrates have revealed that premotor neural circuitry generates a basic rhy...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 9; pp. E2115 - E2124 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
National Academy of Sciences
27-02-2018
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| Series: | PNAS Plus |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Walking is a complex rhythmic locomotor behavior generated by sequential and periodical contraction of muscles essential for coordinated control of movements of legs and leg joints. Studies of walking in vertebrates and invertebrates have revealed that premotor neural circuitry generates a basic rhythmic pattern that is sculpted by sensory feedback and ultimately controls the amplitude and phase of the motor output to leg muscles. However, the identity and functional roles of the premotor interneurons that directly control leg motoneuron activity are poorly understood. Here we take advantage of the powerful genetic methodology available in Drosophila to investigate the role of premotor inhibition in walking by genetically suppressing inhibitory input to leg motoneurons. For this, we have developed an algorithm for automated analysis of leg motion to characterize the walking parameters of wild-type flies from high-speed video recordings. Further, we use genetic reagents for targeted RNAi knockdown of inhibitory neurotransmitter receptors in leg motoneurons together with quantitative analysis of resulting changes in leg movement parameters in freely walking Drosophila. Our findings indicate that targeted down-regulation of the GABAA receptor Rdl (Resistance to Dieldrin) in leg motoneurons results in a dramatic reduction of walking speed and step length without the loss of general leg coordination during locomotion. Genetically restricting the knockdown to the adult stage and subsets of motoneurons yields qualitatively identical results. Taken together, these findings identify GABAergic premotor inhibition of motoneurons as an important determinant of correctly coordinated leg movements and speed of walking in freely behaving Drosophila. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewers: S.A.-T., Harvard Medical School; and C.-F.W., University of Iowa. Contributed by K. VijayRaghavan, January 22, 2018 (sent for review August 7, 2017; reviewed by Spyros Artavanis-Tsakonas and Chun-Fang Wu) 1S.B.M.G. and P.D.P. contributed equally to this work. Author contributions: S.B.M.G., P.D.P., H.R., and K.V. designed research; S.B.M.G., P.D.P., and D.T. performed research; P.D.P., O.V.R., and S.P. contributed new reagents/analytic tools; S.B.M.G., P.D.P., H.R., and K.V. analyzed data; S.B.M.G., P.D.P., H.R., and K.V. wrote the paper; and K.V. mentored the other authors. |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.1713869115 |