A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons

Marieke Meijer, Kristina Rehbach, Jessie W. Brunner, Jessica A. Classen, Hanna C. A. Lammertse, Lola A. van Linge, Desiree Schut, Tamara Krutenko, Matthias Hebisch, L. Niels Cornelisse, Patrick F. Sullivan, Michael Peitz, Ruud F. Toonen, Oliver Brüstle, Matthijs Verhage

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Synaptic dysfunction is associated with many brain disorders, but robust human cell models to study synaptic transmission and plasticity are lacking. Instead, current in vitro studies on human neurons typically rely on spontaneous synaptic events as a proxy for synapse function. Here, we describe a standardized in vitro approach using human neurons cultured individually on glia microdot arrays that allow single-cell analysis of synapse formation and function. We show that single glutamatergic or GABAergic forebrain neurons differentiated from human induced pluripotent stem cells form mature synapses that exhibit robust evoked synaptic transmission. These neurons show plasticity features such as synaptic facilitation, depression, and recovery. Finally, we show that spontaneous events are a poor predictor of synaptic maturity and do not correlate with the robustness of evoked responses. This methodology can be deployed directly to evaluate disease models for synaptic dysfunction and can be leveraged for drug development and precision medicine. This multisite study by Meijer et al. establishes a standardized in vitro approach to study synapse formation and function in single iPSC-derived human neurons. They validate this approach for GABA and glutamatergic human neurons. The methodology is scalable and suitable for compound screening and disease modeling.
Original languageEnglish
Pages (from-to)2199-2211.e6
JournalCell Reports
Volume27
Issue number7
DOIs
Publication statusPublished - 2019

Cite this

Meijer, Marieke ; Rehbach, Kristina ; Brunner, Jessie W. ; Classen, Jessica A. ; Lammertse, Hanna C. A. ; van Linge, Lola A. ; Schut, Desiree ; Krutenko, Tamara ; Hebisch, Matthias ; Cornelisse, L. Niels ; Sullivan, Patrick F. ; Peitz, Michael ; Toonen, Ruud F. ; Brüstle, Oliver ; Verhage, Matthijs. / A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons. In: Cell Reports. 2019 ; Vol. 27, No. 7. pp. 2199-2211.e6.
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abstract = "Synaptic dysfunction is associated with many brain disorders, but robust human cell models to study synaptic transmission and plasticity are lacking. Instead, current in vitro studies on human neurons typically rely on spontaneous synaptic events as a proxy for synapse function. Here, we describe a standardized in vitro approach using human neurons cultured individually on glia microdot arrays that allow single-cell analysis of synapse formation and function. We show that single glutamatergic or GABAergic forebrain neurons differentiated from human induced pluripotent stem cells form mature synapses that exhibit robust evoked synaptic transmission. These neurons show plasticity features such as synaptic facilitation, depression, and recovery. Finally, we show that spontaneous events are a poor predictor of synaptic maturity and do not correlate with the robustness of evoked responses. This methodology can be deployed directly to evaluate disease models for synaptic dysfunction and can be leveraged for drug development and precision medicine. This multisite study by Meijer et al. establishes a standardized in vitro approach to study synapse formation and function in single iPSC-derived human neurons. They validate this approach for GABA and glutamatergic human neurons. The methodology is scalable and suitable for compound screening and disease modeling.",
author = "Marieke Meijer and Kristina Rehbach and Brunner, {Jessie W.} and Classen, {Jessica A.} and Lammertse, {Hanna C. A.} and {van Linge}, {Lola A.} and Desiree Schut and Tamara Krutenko and Matthias Hebisch and Cornelisse, {L. Niels} and Sullivan, {Patrick F.} and Michael Peitz and Toonen, {Ruud F.} and Oliver Br{\"u}stle and Matthijs Verhage",
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doi = "10.1016/j.celrep.2019.04.058",
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Meijer, M, Rehbach, K, Brunner, JW, Classen, JA, Lammertse, HCA, van Linge, LA, Schut, D, Krutenko, T, Hebisch, M, Cornelisse, LN, Sullivan, PF, Peitz, M, Toonen, RF, Brüstle, O & Verhage, M 2019, 'A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons' Cell Reports, vol. 27, no. 7, pp. 2199-2211.e6. https://doi.org/10.1016/j.celrep.2019.04.058

A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons. / Meijer, Marieke; Rehbach, Kristina; Brunner, Jessie W.; Classen, Jessica A.; Lammertse, Hanna C. A.; van Linge, Lola A.; Schut, Desiree; Krutenko, Tamara; Hebisch, Matthias; Cornelisse, L. Niels; Sullivan, Patrick F.; Peitz, Michael; Toonen, Ruud F.; Brüstle, Oliver; Verhage, Matthijs.

In: Cell Reports, Vol. 27, No. 7, 2019, p. 2199-2211.e6.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons

AU - Meijer, Marieke

AU - Rehbach, Kristina

AU - Brunner, Jessie W.

AU - Classen, Jessica A.

AU - Lammertse, Hanna C. A.

AU - van Linge, Lola A.

AU - Schut, Desiree

AU - Krutenko, Tamara

AU - Hebisch, Matthias

AU - Cornelisse, L. Niels

AU - Sullivan, Patrick F.

AU - Peitz, Michael

AU - Toonen, Ruud F.

AU - Brüstle, Oliver

AU - Verhage, Matthijs

PY - 2019

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N2 - Synaptic dysfunction is associated with many brain disorders, but robust human cell models to study synaptic transmission and plasticity are lacking. Instead, current in vitro studies on human neurons typically rely on spontaneous synaptic events as a proxy for synapse function. Here, we describe a standardized in vitro approach using human neurons cultured individually on glia microdot arrays that allow single-cell analysis of synapse formation and function. We show that single glutamatergic or GABAergic forebrain neurons differentiated from human induced pluripotent stem cells form mature synapses that exhibit robust evoked synaptic transmission. These neurons show plasticity features such as synaptic facilitation, depression, and recovery. Finally, we show that spontaneous events are a poor predictor of synaptic maturity and do not correlate with the robustness of evoked responses. This methodology can be deployed directly to evaluate disease models for synaptic dysfunction and can be leveraged for drug development and precision medicine. This multisite study by Meijer et al. establishes a standardized in vitro approach to study synapse formation and function in single iPSC-derived human neurons. They validate this approach for GABA and glutamatergic human neurons. The methodology is scalable and suitable for compound screening and disease modeling.

AB - Synaptic dysfunction is associated with many brain disorders, but robust human cell models to study synaptic transmission and plasticity are lacking. Instead, current in vitro studies on human neurons typically rely on spontaneous synaptic events as a proxy for synapse function. Here, we describe a standardized in vitro approach using human neurons cultured individually on glia microdot arrays that allow single-cell analysis of synapse formation and function. We show that single glutamatergic or GABAergic forebrain neurons differentiated from human induced pluripotent stem cells form mature synapses that exhibit robust evoked synaptic transmission. These neurons show plasticity features such as synaptic facilitation, depression, and recovery. Finally, we show that spontaneous events are a poor predictor of synaptic maturity and do not correlate with the robustness of evoked responses. This methodology can be deployed directly to evaluate disease models for synaptic dysfunction and can be leveraged for drug development and precision medicine. This multisite study by Meijer et al. establishes a standardized in vitro approach to study synapse formation and function in single iPSC-derived human neurons. They validate this approach for GABA and glutamatergic human neurons. The methodology is scalable and suitable for compound screening and disease modeling.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31091456

U2 - 10.1016/j.celrep.2019.04.058

DO - 10.1016/j.celrep.2019.04.058

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JF - Cell Reports

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