dc.contributor.author
Bullmann, Torsten
dc.contributor.author
Kaas, Thomas
dc.contributor.author
Ritzau-Jost, Andreas
dc.contributor.author
Wöhner, Anne
dc.contributor.author
Kirmann, Toni
dc.contributor.author
Rizalar, Filiz Sila
dc.contributor.author
Holzer, Max
dc.contributor.author
Nerlich, Jana
dc.contributor.author
Puchkov, Dmytro
dc.contributor.author
Haucke, Volker
dc.date.accessioned
2024-08-08T12:14:33Z
dc.date.available
2024-08-08T12:14:33Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/44458
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-44170
dc.description.abstract
Understanding the function of the human brain requires determining basic properties of synaptic transmission in human neurons. One of the most fundamental parameters controlling neurotransmitter release is the presynaptic action potential, but its amplitude and duration remain controversial. Presynaptic action potentials have so far been measured with high temporal resolution only in a limited number of vertebrate but not in human neurons. To uncover properties of human presynaptic action potentials, we exploited recently developed tools to generate human glutamatergic neurons by transient expression of Neurogenin 2 (Ngn2) in pluripotent stem cells. During maturation for 3 to 9 weeks of culturing in different established media, the proportion of cells with multiple axon initial segments decreased, while the amount of axonal tau protein and neuronal excitability increased. Super-resolution microscopy revealed the alignment of the pre- and postsynaptic proteins, Bassoon and Homer. Synaptic transmission was surprisingly reliable at frequencies of 20, 50, and 100 Hz. The synchronicity of synaptic transmission during high-frequency transmission increased during 9 weeks of neuronal maturation. To analyze the mechanisms of synchronous high-frequency glutamate release, we developed direct presynaptic patch-clamp recordings from human neurons. The presynaptic action potentials had large overshoots to ∼25 mV and short durations of ∼0.5 ms. Our findings show that Ngn2-induced neurons represent an elegant model system allowing for functional, structural, and molecular analyses of glutamatergic synaptic transmission with high spatiotemporal resolution in human neurons. Furthermore, our data predict that glutamatergic transmission is mediated by large and rapid presynaptic action potentials in the human brain.
en
dc.format.extent
15 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
action potential
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
Human iPSC-Derived Neurons with Reliable Synapses and Large Presynaptic Action Potentials
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
e0971232024
dcterms.bibliographicCitation.doi
10.1523/JNEUROSCI.0971-23.2024
dcterms.bibliographicCitation.journaltitle
Journal of Neuroscience
dcterms.bibliographicCitation.number
24
dcterms.bibliographicCitation.volume
44
dcterms.bibliographicCitation.url
https://doi.org/10.1523/JNEUROSCI.0971-23.2024
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie
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refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1529-2401
refubium.resourceType.provider
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