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Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture

Neurological disorders display a broad spectrum of clinical manifestations. Yet, at the cellular level, virtually all these diseases converge into a common phenotype of dysregulated synaptic connectivity. In dementia, synapse dysfunction precedes neurodegeneration and cognitive impairment by several...

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Autores principales: Verstraelen, Peter, Van Dyck, Michiel, Verschuuren, Marlies, Kashikar, Nachiket D., Nuydens, Rony, Timmermans, Jean-Pierre, De Vos, Winnok H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028601/
https://www.ncbi.nlm.nih.gov/pubmed/29997468
http://dx.doi.org/10.3389/fnins.2018.00389
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author Verstraelen, Peter
Van Dyck, Michiel
Verschuuren, Marlies
Kashikar, Nachiket D.
Nuydens, Rony
Timmermans, Jean-Pierre
De Vos, Winnok H.
author_facet Verstraelen, Peter
Van Dyck, Michiel
Verschuuren, Marlies
Kashikar, Nachiket D.
Nuydens, Rony
Timmermans, Jean-Pierre
De Vos, Winnok H.
author_sort Verstraelen, Peter
collection PubMed
description Neurological disorders display a broad spectrum of clinical manifestations. Yet, at the cellular level, virtually all these diseases converge into a common phenotype of dysregulated synaptic connectivity. In dementia, synapse dysfunction precedes neurodegeneration and cognitive impairment by several years, making the synapse a crucial entry point for the development of diagnostic and therapeutic strategies. Whereas high-resolution imaging and biochemical fractionations yield detailed insight into the molecular composition of the synapse, standardized assays are required to quickly gauge synaptic connectivity across large populations of cells under a variety of experimental conditions. Such screening capabilities have now become widely accessible with the advent of high-throughput, high-content microscopy. In this review, we discuss how microscopy-based approaches can be used to extract quantitative information about synaptic connectivity in primary neurons with deep coverage. We elaborate on microscopic readouts that may serve as a proxy for morphofunctional connectivity and we critically analyze their merits and limitations. Finally, we allude to the potential of alternative culture paradigms and integrative approaches to enable comprehensive profiling of synaptic connectivity.
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spelling pubmed-60286012018-07-11 Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture Verstraelen, Peter Van Dyck, Michiel Verschuuren, Marlies Kashikar, Nachiket D. Nuydens, Rony Timmermans, Jean-Pierre De Vos, Winnok H. Front Neurosci Neuroscience Neurological disorders display a broad spectrum of clinical manifestations. Yet, at the cellular level, virtually all these diseases converge into a common phenotype of dysregulated synaptic connectivity. In dementia, synapse dysfunction precedes neurodegeneration and cognitive impairment by several years, making the synapse a crucial entry point for the development of diagnostic and therapeutic strategies. Whereas high-resolution imaging and biochemical fractionations yield detailed insight into the molecular composition of the synapse, standardized assays are required to quickly gauge synaptic connectivity across large populations of cells under a variety of experimental conditions. Such screening capabilities have now become widely accessible with the advent of high-throughput, high-content microscopy. In this review, we discuss how microscopy-based approaches can be used to extract quantitative information about synaptic connectivity in primary neurons with deep coverage. We elaborate on microscopic readouts that may serve as a proxy for morphofunctional connectivity and we critically analyze their merits and limitations. Finally, we allude to the potential of alternative culture paradigms and integrative approaches to enable comprehensive profiling of synaptic connectivity. Frontiers Media S.A. 2018-06-26 /pmc/articles/PMC6028601/ /pubmed/29997468 http://dx.doi.org/10.3389/fnins.2018.00389 Text en Copyright © 2018 Verstraelen, Van Dyck, Verschuuren, Kashikar, Nuydens, Timmermans and De Vos. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Verstraelen, Peter
Van Dyck, Michiel
Verschuuren, Marlies
Kashikar, Nachiket D.
Nuydens, Rony
Timmermans, Jean-Pierre
De Vos, Winnok H.
Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture
title Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture
title_full Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture
title_fullStr Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture
title_full_unstemmed Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture
title_short Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture
title_sort image-based profiling of synaptic connectivity in primary neuronal cell culture
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028601/
https://www.ncbi.nlm.nih.gov/pubmed/29997468
http://dx.doi.org/10.3389/fnins.2018.00389
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