Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord
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
Affiliations
Jonathan J. Milla-Cruz
Hotchkiss 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
Adam P. Lognon
Hotchkiss 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
Michelle A. Tran
Hotchkiss 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
Stephanie A. Di Vito
Hotchkiss 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
Carlotta Löer
School of Psychology and Neuroscience, University of St Andrews, Fife KY16 9JP, UK
Anchita Shonak
Hotchkiss 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
Matthew J. Broadhead
School of Psychology and Neuroscience, University of St Andrews, Fife KY16 9JP, UK
Gareth B. Miles
School of Psychology and Neuroscience, University of St Andrews, Fife KY16 9JP, UK
Simon A. Sharples
Division of Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Corresponding author
Patrick J. Whelan
Hotchkiss 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 author
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.
