Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction
The Drosophila neuromuscular system is widely used to characterize synaptic development and function. However, little is known about how specific synaptic alterations effect neuromuscular transduction and muscle contractility, which ultimately dictate behavioural output. Here we develop and use a fo...
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| 格式: | 文件 |
| 语言: | English |
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Wiley
2022
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| 在线阅读: | https://hdl.handle.net/1721.1/146893 |
| _version_ | 1826196516450074624 |
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| author | Ormerod, Kiel G Scibelli, Anthony E Littleton, J Troy |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ormerod, Kiel G Scibelli, Anthony E Littleton, J Troy |
| author_sort | Ormerod, Kiel G |
| collection | MIT |
| description | The Drosophila neuromuscular system is widely used to characterize synaptic development and function. However, little is known about how specific synaptic alterations effect neuromuscular transduction and muscle contractility, which ultimately dictate behavioural output. Here we develop and use a force transducer system to characterize excitation-contraction coupling at Drosophila larval neuromuscular junctions (NMJs), examining how specific neuronal and muscle manipulations disrupt muscle contractility. Muscle contraction force increased with motoneuron stimulation frequency and duration, showing considerable plasticity between 5 and 40 Hz and saturating above 50 Hz. Endogenous recordings of fictive contractions revealed average motoneuron burst frequencies of 20-30 Hz, consistent with the system operating within this plastic range of contractility. Temperature was also a key factor in muscle contractility, as force was enhanced at lower temperatures and dramatically reduced with increasing temperatures. Pharmacological and genetic manipulations of critical components of Ca2+ regulation in both pre- and postsynaptic compartments affected the strength and time course of muscle contractions. A screen for modulators of muscle contractility led to identification and characterization of the molecular and cellular pathway by which the FMRFa peptide, TPAEDFMRFa, increases muscle performance. These findings indicate Drosophila NMJs provide a robust system to correlate synaptic dysfunction, regulation and modulation to alterations in excitation-contraction coupling. KEY POINTS: Larval muscle contraction force increases with stimulation frequency and duration, revealing substantial plasticity between 5 and 40 Hz. Fictive contraction recordings demonstrate endogenous motoneuron burst frequencies consistent with the neuromuscular system operating within the range of greatest plasticity. Genetic and pharmacological manipulations of critical components of pre- and postsynaptic Ca2+ regulation significantly affect the strength and time course of muscle contractions. A screen for modulators of the excitation-contraction machinery identified a FMRFa peptide, TPAEDFMRFa and its associated signalling pathway, that dramatically increases muscle performance. Drosophila serves as an excellent model for dissecting components of the excitation-contraction coupling machinery. |
| first_indexed | 2024-09-23T10:28:35Z |
| format | Article |
| id | mit-1721.1/146893 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:28:35Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1468932022-12-16T03:35:36Z Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction Ormerod, Kiel G Scibelli, Anthony E Littleton, J Troy Massachusetts Institute of Technology. Department of Biology The Drosophila neuromuscular system is widely used to characterize synaptic development and function. However, little is known about how specific synaptic alterations effect neuromuscular transduction and muscle contractility, which ultimately dictate behavioural output. Here we develop and use a force transducer system to characterize excitation-contraction coupling at Drosophila larval neuromuscular junctions (NMJs), examining how specific neuronal and muscle manipulations disrupt muscle contractility. Muscle contraction force increased with motoneuron stimulation frequency and duration, showing considerable plasticity between 5 and 40 Hz and saturating above 50 Hz. Endogenous recordings of fictive contractions revealed average motoneuron burst frequencies of 20-30 Hz, consistent with the system operating within this plastic range of contractility. Temperature was also a key factor in muscle contractility, as force was enhanced at lower temperatures and dramatically reduced with increasing temperatures. Pharmacological and genetic manipulations of critical components of Ca2+ regulation in both pre- and postsynaptic compartments affected the strength and time course of muscle contractions. A screen for modulators of muscle contractility led to identification and characterization of the molecular and cellular pathway by which the FMRFa peptide, TPAEDFMRFa, increases muscle performance. These findings indicate Drosophila NMJs provide a robust system to correlate synaptic dysfunction, regulation and modulation to alterations in excitation-contraction coupling. KEY POINTS: Larval muscle contraction force increases with stimulation frequency and duration, revealing substantial plasticity between 5 and 40 Hz. Fictive contraction recordings demonstrate endogenous motoneuron burst frequencies consistent with the neuromuscular system operating within the range of greatest plasticity. Genetic and pharmacological manipulations of critical components of pre- and postsynaptic Ca2+ regulation significantly affect the strength and time course of muscle contractions. A screen for modulators of the excitation-contraction machinery identified a FMRFa peptide, TPAEDFMRFa and its associated signalling pathway, that dramatically increases muscle performance. Drosophila serves as an excellent model for dissecting components of the excitation-contraction coupling machinery. 2022-12-15T18:56:44Z 2022-12-15T18:56:44Z 2022 2022-12-15T18:45:01Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146893 Ormerod, Kiel G, Scibelli, Anthony E and Littleton, J Troy. 2022. "Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction." Journal of Physiology, 600 (2). en 10.1113/JP282092 Journal of Physiology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley PMC |
| spellingShingle | Ormerod, Kiel G Scibelli, Anthony E Littleton, J Troy Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction |
| title | Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction |
| title_full | Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction |
| title_fullStr | Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction |
| title_full_unstemmed | Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction |
| title_short | Regulation of excitation‐contraction coupling at the Drosophila neuromuscular junction |
| title_sort | regulation of excitation contraction coupling at the drosophila neuromuscular junction |
| url | https://hdl.handle.net/1721.1/146893 |
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