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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.
Afiliação
  • Meijer M; Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • Rehbach K; Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany; LIFE&BRAIN GmbH, Cellomics Unit, 53127 Bonn, Germany.
  • Brunner JW; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • Classen JA; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • Lammertse HCA; Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • van Linge LA; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • Schut D; Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • Krutenko T; Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany.
  • Hebisch M; Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany.
  • Cornelisse LN; Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • Sullivan PF; UNC Center for Psychiatric Genomics, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599-7160, USA; Karolinska Institutet, Department of Medical Epidemiology and Biostatistics and Department of (Clinical) Genetics, Nobels Väg 12A, 171 77 Stockholm, Sweden.
  • Peitz M; Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany; Cell Programming Core Facility, University of Bonn School of Medicine, Bonn, Germany. Electronic address: peitz@uni-bonn.de.
  • Toonen RF; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
  • Brüstle O; Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany. Electronic address: brustle@uni-bonn.de.
  • Verhage M; Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amst
Cell Rep ; 27(7): 2199-2211.e6, 2019 05 14.
Article em En | MEDLINE | ID: mdl-31091456
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transmissão Sináptica / Neurogênese / Células-Tronco Pluripotentes Induzidas / Análise de Célula Única / Neurônios GABAérgicos / Plasticidade Neuronal Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transmissão Sináptica / Neurogênese / Células-Tronco Pluripotentes Induzidas / Análise de Célula Única / Neurônios GABAérgicos / Plasticidade Neuronal Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Holanda