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


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.

Authors Fenske P, Grauel MK, Brockmann MM, Dorrn AL, Trimbuch T, Rosenmund C
Journal Scientific reports
Publication Date 2019 Mar 20;9(1):4890
PubMed 30894602
PubMed Central PMC6427022
DOI 10.1038/s41598-019-41259-1

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