title: Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.
abstract: Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, Austria ; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Illes
authors.affiliation: Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Jakab
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Beyer
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, Austria ; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Gelfert
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, Austria ; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria ; Institute of Experimental Neuroregeneration, Paracelsus Medical University, 5020 Salzburg, Austria.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Couillard-Despres
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Schnitzler
authors.affiliation: Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Ritter
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, Austria ; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
mesh_terms: D000200:Action Potentials; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002454:Cell Differentiation; D005347:Fibroblasts / Q000378:metabolism; D006329:Heart Conduction System / Q000166:cytology*; D053605:Leukemia Inhibitory Factor; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D053605:Leukemia Inhibitory Factor; D015222:Sodium Channels