Neuroepithelial progenitors generate and propagate non-neuronal action potentials across the spinal cord

• Published in: Current biology Vol. 31; no. 20; pp. 4584 - 4595.e4
• Main Authors: Arulkandarajah, Kalaimakan Hervé, Osterstock, Guillaume, Lafont, Agathe, Le Corronc, Hervé, Escalas, Nathalie, Corsini, Silvia, Le Bras, Barbara, Chenane, Linda, Boeri, Juliette, Czarnecki, Antonny, Mouffle, Christine, Bullier, Erika, Hong, Elim, Soula, Cathy, Legendre, Pascal, Mangin, Jean-Marie
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 25-10-2021; Elsevier
• Subjects: Action Potentials - physiology; Animals; ATP; Calcium Channels; calcium imaging; connexins; electrophysiology; Gap Junctions; glia; Life Sciences; Mice; motor behavior; Motor Neurons - physiology; neural stem cells; optogenetics; spinal cord; Spinal Cord - physiology; voltage-gated calcium channels; electrophysiology; motor behavior; neural stem cells; optogenetics; voltage-gated calcium channels; spinal cord; connexins; glia; calcium imaging; ATP
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2021.08.019

In the developing central nervous system, electrical signaling is thought to rely exclusively on differentiating neurons as they acquire the ability to generate and propagate action potentials. Accordingly, neuroepithelial progenitors (NEPs), which give rise to all neurons and glial cells during development, have been reported to remain electrically passive. Here, we investigated the physiological properties of NEPs at the onset of spontaneous neural activity (SNA) initiating motor behavior in mouse embryonic spinal cord. Using patch-clamp recordings, we discovered that spinal NEPs exhibit spontaneous membrane depolarizations during episodes of SNA. These rhythmic depolarizations exhibited a ventral-to-dorsal gradient with the highest amplitude located in the floor plate, the ventral-most part of the neuroepithelium. Paired recordings revealed that NEPs are coupled via gap junctions and form an electrical syncytium. Although other NEPs were electrically passive, we discovered that floor-plate NEPs generated large Na+/Ca2+ action potentials. Unlike in neurons, floor-plate action potentials relied primarily on the activation of voltage-gated T-type calcium channels (TTCCs). In situ hybridization showed that all 3 known subtypes of TTCCs are predominantly expressed in the floor plate. During SNA, we found that acetylcholine released by motoneurons rhythmically triggers floor-plate action potentials by acting through nicotinic acetylcholine receptors. Finally, by expressing the genetically encoded calcium indicator GCaMP6f in the floor plate, we demonstrated that neuroepithelial action potentials are associated with calcium waves and propagate along the entire length of the spinal cord. Our work reveals a novel physiological mechanism to generate and propagate electrical signals across a neural structure independently from neurons.
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•Neuroepithelial progenitors (NEPs) are depolarized by spontaneous neural activity•NEPs form a single electrical syncytium connected by gap junctions•Floor-plate NEPs generate Na+/Ca2+ action potentials in response to acetylcholine•Neuroepithelial action potentials propagate across the entire spinal cord
Arulkandarajah et al. use electrophysiology, optogenetics, and calcium imaging to show that neuroepithelial progenitors in the floor plate generate Na+/Ca2+ action potentials in response to cholinergic signaling and propagate electrical signals across the embryonic spinal cord via connexins and purinergic signaling acting through P2X7R.