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Verstraelen P, Van Dyck M, Verschuuren M, et al. Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture. Front Neurosci. 2018;12:389doi: 10.3389/fnins.2018.00389.
Verstraelen, P., Van Dyck, M., Verschuuren, M., Kashikar, N. D., Nuydens, R., Timmermans, J. P., & De Vos, W. H. (2018). Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture. Frontiers in neuroscience, 12389. https://doi.org/10.3389/fnins.2018.00389
Verstraelen, Peter, et al. "Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture." Frontiers in neuroscience vol. 12 (2018): 389. doi: https://doi.org/10.3389/fnins.2018.00389
Verstraelen P, Van Dyck M, Verschuuren M, Kashikar ND, Nuydens R, Timmermans JP, De Vos WH. Image-Based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture. Front Neurosci. 2018 Jun 26;12:389. doi: 10.3389/fnins.2018.00389. eCollection 2018. PMID: 29997468; PMCID: PMC6028601.
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Front Neurosci. 2018 Jun 26;12:389. doi: 10.3389/fnins.2018.00389. eCollection 2018.

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

Frontiers in neuroscience

Peter Verstraelen, Michiel Van Dyck, Marlies Verschuuren, Nachiket D Kashikar, Rony Nuydens, Jean-Pierre Timmermans, Winnok H De Vos

Affiliations

  1. Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
  2. Janssen Research and Development, Janssen Pharmaceutica N.V., Beerse, Belgium.
  3. Cell Systems and Imaging, Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.

PMID: 29997468 PMCID: PMC6028601 DOI: 10.3389/fnins.2018.00389

Abstract

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.

Keywords: dendritic spine; fluorescent labeling; high-content screening; image analysis; morphofunctional connectivity; primary neuronal culture; synapse

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