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

Title: Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
Authors: Pascal Fenske; M. Katharina Grauel; Marisa M. Brockmann; Anja L. Dorrn; Thorsten Trimbuch; Christian Rosenmund
Source: Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
Publisher Information: Nature Portfolio, 2019.
Publication Year: 2019
Collection: LCC:Medicine; LCC:Science
Subject Terms: Medicine; Science
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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-019-41259-1
Access URL: https://doaj.org/article/a865c8d717e04bdcb85579ff705a28ef
Accession Number: edsdoj.865c8d717e04bdcb85579ff705a28ef
Database: Directory of Open Access Journals