RT Journal Article
SR Electronic
T1 Neuroepithelial progenitors generate and propagate non-neuronal action potentials across the spinal cord
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.23.111955
DO 10.1101/2020.05.23.111955
A1 Kalaimakan Hervé Arulkandarajah
A1 Guillaume Osterstock
A1 Agathe Lafont
A1 Hervé Le Corronc
A1 Nathalie Escalas
A1 Silvia Corsini
A1 Barbara Le Bras
A1 Juliette Boeri
A1 Antonny Czarnecki
A1 Christine Mouffle
A1 Erika Bullier
A1 Elim Hong
A1 Cathy Soula
A1 Pascal Legendre
A1 Jean-Marie Mangin
YR 2020
UL http://biorxiv.org/content/early/2020/12/22/2020.05.23.111955.abstract
AB In the developing central nervous system, electrical signaling is thought to rely exclusively on differentiating neurons as they acquire the ability to generate action potentials. Accordingly, the neuroepithelial progenitors (NEPs) giving rise to all neurons and glial cells during development have been reported to remain electrically passive. Here, we investigated the physiological properties of NEPs in the mouse spinal cord at the onset of spontaneous neural activity (SNA) initiating motor behavior in embryos. Using patch-clamp recordings, we discovered that spinal NEPs exhibit spontaneous membrane depolarizations during episodes of SNA. These recurrent 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 extensively coupled via gap-junctions and form a single electrical syncytium. Although other NEPs were electrically passive, we discovered that floor-plate NEPs have the unique ability to generate large Na+/Ca++ action potentials. Unlike 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 highly and predominantly expressed in the floor-plate. During SNA, we found that acetylcholine released by motoneurons recurrently trigger 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. By unraveling a novel physiological mechanism generating electrical signals which can propagate independently from neurons across a neural structure, our work significantly changes our understanding of the development, origin and extent of electrical signaling in the central nervous system.HIGHLIGHTSSpinal neuroepithelial progenitors (NEP) are depolarized during spontaneous neural activityNEPs form a single electrical syncytium connected by gap junctionsFloor-plate NEPs generate large Na+/Ca++ action potentials in response to acetylcholineNeuroepithelial action potentials propagate across the entire spinal cordCompeting Interest StatementThe authors have declared no competing interest.