Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology

Abstract Recently developed technology to differentiate induced pluripotent stem cells (iPSCs) into human induced neurons (iNs) provides an exciting opportunity to study the function of human neurons. However, functional characterisations of iNs have been hampered by the reliance on mass culturing p...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pascal Fenske, M. Katharina Grauel, Marisa M. Brockmann, Anja L. Dorrn, Thorsten Trimbuch, Christian Rosenmund
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a865c8d717e04bdcb85579ff705a28ef
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a865c8d717e04bdcb85579ff705a28ef
record_format	dspace
spelling	oai:doaj.org-article:a865c8d717e04bdcb85579ff705a28ef2021-12-02T16:08:53ZAutaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology10.1038/s41598-019-41259-12045-2322https://doaj.org/article/a865c8d717e04bdcb85579ff705a28ef2019-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-41259-1https://doaj.org/toc/2045-2322Abstract Recently developed technology to differentiate induced pluripotent stem cells (iPSCs) into human induced neurons (iNs) provides an exciting opportunity to study the function of human neurons. However, functional characterisations of iNs have been hampered by the reliance on mass culturing protocols which do not allow assessment of synaptic release characteristics and neuronal morphology at the individual cell level with quantitative precision. Here, we have developed for the first time a protocol to generate autaptic cultures of iPSC-derived iNs. We show that our method efficiently generates mature, autaptic iNs with robust spontaneous and action potential-driven synaptic transmission. The synaptic responses are sensitive to modulation by metabotropic receptor agonists as well as potentiation by acute phorbol ester application. Finally, we demonstrate loss of evoked and spontaneous release by Unc13A knockdown. This culture system provides a versatile platform allowing for quantitative and integrative assessment of morphophysiological and molecular parameters underlying human synaptic transmission.Pascal FenskeM. Katharina GrauelMarisa M. BrockmannAnja L. DorrnThorsten TrimbuchChristian RosenmundNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pascal Fenske M. Katharina Grauel Marisa M. Brockmann Anja L. Dorrn Thorsten Trimbuch Christian Rosenmund Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
description	Abstract Recently developed technology to differentiate induced pluripotent stem cells (iPSCs) into human induced neurons (iNs) provides an exciting opportunity to study the function of human neurons. However, functional characterisations of iNs have been hampered by the reliance on mass culturing protocols which do not allow assessment of synaptic release characteristics and neuronal morphology at the individual cell level with quantitative precision. Here, we have developed for the first time a protocol to generate autaptic cultures of iPSC-derived iNs. We show that our method efficiently generates mature, autaptic iNs with robust spontaneous and action potential-driven synaptic transmission. The synaptic responses are sensitive to modulation by metabotropic receptor agonists as well as potentiation by acute phorbol ester application. Finally, we demonstrate loss of evoked and spontaneous release by Unc13A knockdown. This culture system provides a versatile platform allowing for quantitative and integrative assessment of morphophysiological and molecular parameters underlying human synaptic transmission.
format	article
author	Pascal Fenske M. Katharina Grauel Marisa M. Brockmann Anja L. Dorrn Thorsten Trimbuch Christian Rosenmund
author_facet	Pascal Fenske M. Katharina Grauel Marisa M. Brockmann Anja L. Dorrn Thorsten Trimbuch Christian Rosenmund
author_sort	Pascal Fenske
title	Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
title_short	Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
title_full	Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
title_fullStr	Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
title_full_unstemmed	Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
title_sort	autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/a865c8d717e04bdcb85579ff705a28ef
work_keys_str_mv	AT pascalfenske autapticculturesofhumaninducedneuronsasaversatileplatformforstudyingsynapticfunctionandneuronalmorphology AT mkatharinagrauel autapticculturesofhumaninducedneuronsasaversatileplatformforstudyingsynapticfunctionandneuronalmorphology AT marisambrockmann autapticculturesofhumaninducedneuronsasaversatileplatformforstudyingsynapticfunctionandneuronalmorphology AT anjaldorrn autapticculturesofhumaninducedneuronsasaversatileplatformforstudyingsynapticfunctionandneuronalmorphology AT thorstentrimbuch autapticculturesofhumaninducedneuronsasaversatileplatformforstudyingsynapticfunctionandneuronalmorphology AT christianrosenmund autapticculturesofhumaninducedneuronsasaversatileplatformforstudyingsynapticfunctionandneuronalmorphology
_version_	1718384488734523392

Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology

Ejemplares similares