Milla-Cruz Jonathan J, Lognon Adam P, Tran Michelle A, Di Vito Stephanie A, Löer Carlotta, Shonak Anchita, Broadhead Matthew J, Miles Gareth B, Sharples Simon A, Whelan Patrick J
Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada.
iScience. 2025 Feb 7;28(3):111971. doi: 10.1016/j.isci.2025.111971. eCollection 2025 Mar 21.
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, GABA 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.
脊髓回路产生运动节律，但间歇性运动行为背后的机制仍不清楚。本研究调查了多巴胺诱导的离体新生小鼠脊髓中的间歇性节律，以了解这些机制。尽管偶尔会观察到异步现象，但间歇性节律通常是同步的，并沿头尾方向传播。对L5背根的电刺激夹带了间歇性节律，提示传入控制和分布式网络。即使在横断或腹外侧索（VLF）损伤后，间歇性活动仍在离体的胸段或骶段持续存在，这意味着VLF耦合网络。在VLF和背根轴突中观察到节律性，并且独立于通过运动神经元、GABA受体或背侧抑制回路的胆碱能兴奋。这些发现表明，一个灵活耦合的分布式脊髓中间神经元网络是间歇性节律的基础，为未来研究脊髓回路如何被调节以产生多样化的运动输出提供了基础。
