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Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease

Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational...

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Autores principales: Schwarz, Niklas, Uysal, Betül, Welzer, Marc, Bahr, Jacqueline C, Layer, Nikolas, Löffler, Heidi, Stanaitis, Kornelijus, PA, Harshad, Weber, Yvonne G, Hedrich, Ulrike BS, Honegger, Jürgen B, Skodras, Angelos, Becker, Albert J, Wuttke, Thomas V, Koch, Henner
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733599/
https://www.ncbi.nlm.nih.gov/pubmed/31498083
http://dx.doi.org/10.7554/eLife.48417
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author Schwarz, Niklas
Uysal, Betül
Welzer, Marc
Bahr, Jacqueline C
Layer, Nikolas
Löffler, Heidi
Stanaitis, Kornelijus
PA, Harshad
Weber, Yvonne G
Hedrich, Ulrike BS
Honegger, Jürgen B
Skodras, Angelos
Becker, Albert J
Wuttke, Thomas V
Koch, Henner
author_facet Schwarz, Niklas
Uysal, Betül
Welzer, Marc
Bahr, Jacqueline C
Layer, Nikolas
Löffler, Heidi
Stanaitis, Kornelijus
PA, Harshad
Weber, Yvonne G
Hedrich, Ulrike BS
Honegger, Jürgen B
Skodras, Angelos
Becker, Albert J
Wuttke, Thomas V
Koch, Henner
author_sort Schwarz, Niklas
collection PubMed
description Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling ‘high throughput’ fluorescence-mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro. This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry.
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spelling pubmed-67335992019-09-11 Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease Schwarz, Niklas Uysal, Betül Welzer, Marc Bahr, Jacqueline C Layer, Nikolas Löffler, Heidi Stanaitis, Kornelijus PA, Harshad Weber, Yvonne G Hedrich, Ulrike BS Honegger, Jürgen B Skodras, Angelos Becker, Albert J Wuttke, Thomas V Koch, Henner eLife Neuroscience Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling ‘high throughput’ fluorescence-mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro. This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry. eLife Sciences Publications, Ltd 2019-09-09 /pmc/articles/PMC6733599/ /pubmed/31498083 http://dx.doi.org/10.7554/eLife.48417 Text en © 2019, Schwarz et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Schwarz, Niklas
Uysal, Betül
Welzer, Marc
Bahr, Jacqueline C
Layer, Nikolas
Löffler, Heidi
Stanaitis, Kornelijus
PA, Harshad
Weber, Yvonne G
Hedrich, Ulrike BS
Honegger, Jürgen B
Skodras, Angelos
Becker, Albert J
Wuttke, Thomas V
Koch, Henner
Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease
title Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease
title_full Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease
title_fullStr Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease
title_full_unstemmed Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease
title_short Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease
title_sort long-term adult human brain slice cultures as a model system to study human cns circuitry and disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733599/
https://www.ncbi.nlm.nih.gov/pubmed/31498083
http://dx.doi.org/10.7554/eLife.48417
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