Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord

Summary: Spinal circuits generate locomotor rhythms, but the mechanisms behind episodic locomotor behaviors remain unclear. This study investigated dopamine-induced episodic rhythms in isolated neonatal mouse spinal cords to understand these mechanisms. The episodic rhythms were generally synchronou...

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Main Authors: Jonathan J. Milla-Cruz, Adam P. Lognon, Michelle A. Tran, Stephanie A. Di Vito, Carlotta Löer, Anchita Shonak, Matthew J. Broadhead, Gareth B. Miles, Simon A. Sharples, Patrick J. Whelan
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Language:English
Published: Elsevier 2025-03-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225002317
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author Jonathan J. Milla-Cruz
Adam P. Lognon
Michelle A. Tran
Stephanie A. Di Vito
Carlotta Löer
Anchita Shonak
Matthew J. Broadhead
Gareth B. Miles
Simon A. Sharples
Patrick J. Whelan
author_facet Jonathan J. Milla-Cruz
Adam P. Lognon
Michelle A. Tran
Stephanie A. Di Vito
Carlotta Löer
Anchita Shonak
Matthew J. Broadhead
Gareth B. Miles
Simon A. Sharples
Patrick J. Whelan
author_sort Jonathan J. Milla-Cruz
collection DOAJ
description Summary: Spinal circuits generate locomotor rhythms, but the mechanisms behind episodic locomotor behaviors remain unclear. This study investigated dopamine-induced episodic rhythms in isolated neonatal mouse spinal cords to understand these mechanisms. The episodic rhythms were generally synchronous and propagated rostro-caudally, although occasional asynchrony was observed. Electrical stimulation of the L5 dorsal root entrained the episodic rhythms, suggesting afferent control and a distributed network. Even after transection or ventrolateral funiculus (VLF) lesions, episodic activity persisted in isolated thoracic or sacral segments, implying VLF-coupled networks. Rhythmicity was observed in VLF and dorsal root axons and was independent of cholinergic excitation via motoneurons, GABAA receptors, or dorsal inhibitory circuits. These findings suggest a flexibly coupled, distributed spinal interneuron network underlies episodic rhythmicity, providing a foundation for future investigations into how spinal circuits are modulated to produce diverse motor outputs.
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issn 2589-0042
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publishDate 2025-03-01
publisher Elsevier
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series iScience
spelling doaj-art-226d9cc4941c4548a0addedf8fe7470e2025-08-20T03:00:34ZengElsevieriScience2589-00422025-03-0128311197110.1016/j.isci.2025.111971Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cordJonathan J. Milla-Cruz0Adam P. Lognon1Michelle A. Tran2Stephanie A. Di Vito3Carlotta Löer4Anchita Shonak5Matthew J. Broadhead6Gareth B. Miles7Simon A. Sharples8Patrick J. Whelan9Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB T2N 1N4, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB T2N 1N4, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB T2N 1N4, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB T2N 1N4, CanadaSchool of Psychology and Neuroscience, University of St Andrews, Fife KY16 9JP, UKHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB T2N 1N4, CanadaSchool of Psychology and Neuroscience, University of St Andrews, Fife KY16 9JP, UKSchool of Psychology and Neuroscience, University of St Andrews, Fife KY16 9JP, UKDivision of Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Corresponding authorHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada; Corresponding authorSummary: Spinal circuits generate locomotor rhythms, but the mechanisms behind episodic locomotor behaviors remain unclear. This study investigated dopamine-induced episodic rhythms in isolated neonatal mouse spinal cords to understand these mechanisms. The episodic rhythms were generally synchronous and propagated rostro-caudally, although occasional asynchrony was observed. Electrical stimulation of the L5 dorsal root entrained the episodic rhythms, suggesting afferent control and a distributed network. Even after transection or ventrolateral funiculus (VLF) lesions, episodic activity persisted in isolated thoracic or sacral segments, implying VLF-coupled networks. Rhythmicity was observed in VLF and dorsal root axons and was independent of cholinergic excitation via motoneurons, GABAA receptors, or dorsal inhibitory circuits. These findings suggest a flexibly coupled, distributed spinal interneuron network underlies episodic rhythmicity, providing a foundation for future investigations into how spinal circuits are modulated to produce diverse motor outputs.http://www.sciencedirect.com/science/article/pii/S2589004225002317NeuroscienceMolecular neuroscienceSensory neuroscience
spellingShingle Jonathan J. Milla-Cruz
Adam P. Lognon
Michelle A. Tran
Stephanie A. Di Vito
Carlotta Löer
Anchita Shonak
Matthew J. Broadhead
Gareth B. Miles
Simon A. Sharples
Patrick J. Whelan
Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
iScience
Neuroscience
Molecular neuroscience
Sensory neuroscience
title Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
title_full Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
title_fullStr Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
title_full_unstemmed Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
title_short Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
title_sort episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
topic Neuroscience
Molecular neuroscience
Sensory neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004225002317
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