Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations

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 presen...

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Main Authors: Sebastian Illes, Martin Jakab, Felix Beyer, Renate Gelfert, Sébastien Couillard-Despres, Alfons Schnitzler, Markus Ritter, Ludwig Aigner
Format: Article
Language:English
Published: Elsevier 2014-03-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221367111400023X
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author Sebastian Illes
Martin Jakab
Felix Beyer
Renate Gelfert
Sébastien Couillard-Despres
Alfons Schnitzler
Markus Ritter
Ludwig Aigner
author_facet Sebastian Illes
Martin Jakab
Felix Beyer
Renate Gelfert
Sébastien Couillard-Despres
Alfons Schnitzler
Markus Ritter
Ludwig Aigner
author_sort Sebastian Illes
collection DOAJ
description 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.
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spelling doaj.art-79c16dc1226148279d532ee63d657e192022-12-22T01:06:15ZengElsevierStem Cell Reports2213-67112014-03-012332333610.1016/j.stemcr.2014.01.006Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal PopulationsSebastian Illes0Martin Jakab1Felix Beyer2Renate Gelfert3Sébastien Couillard-Despres4Alfons Schnitzler5Markus Ritter6Ludwig Aigner7Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, AustriaInstitute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, AustriaInstitute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, AustriaInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, AustriaInstitute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, AustriaInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria, AustriaNeurons 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.http://www.sciencedirect.com/science/article/pii/S221367111400023X
spellingShingle Sebastian Illes
Martin Jakab
Felix Beyer
Renate Gelfert
Sébastien Couillard-Despres
Alfons Schnitzler
Markus Ritter
Ludwig Aigner
Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations
Stem Cell Reports
title Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations
title_full Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations
title_fullStr Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations
title_full_unstemmed Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations
title_short Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations
title_sort intrinsically active and pacemaker neurons in pluripotent stem cell derived neuronal populations
url http://www.sciencedirect.com/science/article/pii/S221367111400023X
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