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Image-based profiling of synaptic connectivity in primary neuronal cell culture

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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
LONG-TERM POTENTIATION, GREEN FLUORESCENT PROTEIN, AMYLOID-BETA, OLIGOMERS, DENDRITIC SPINE LOSS, IN-VIVO, HIPPOCAMPAL-NEURONS, ALZHEIMERS-DISEASE, AMPA RECEPTORS, OXIDATIVE STRESS, DRUG DISCOVERY, primary neuronal culture, synapse, dendritic spine, image analysis, morphofunctional connectivity, fluorescent labeling, high-content, screening

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Chicago
Verstraelen, Peter, Michiel Van Dyck, Marlies Verschuuren, Nachiket D Kashikar, Rony Nuydens, Jean-Pierre Timmermans, and Winnok De Vos. 2018. “Image-based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture.” Frontiers in Neuroscience 12.
APA
Verstraelen, P., Van Dyck, M., Verschuuren, M., Kashikar, N. D., Nuydens, R., Timmermans, J.-P., & De Vos, W. (2018). Image-based profiling of synaptic connectivity in primary neuronal cell culture. FRONTIERS IN NEUROSCIENCE, 12.
Vancouver
1.
Verstraelen P, Van Dyck M, Verschuuren M, Kashikar ND, Nuydens R, Timmermans J-P, et al. Image-based profiling of synaptic connectivity in primary neuronal cell culture. FRONTIERS IN NEUROSCIENCE. 2018;12.
MLA
Verstraelen, Peter et al. “Image-based Profiling of Synaptic Connectivity in Primary Neuronal Cell Culture.” FRONTIERS IN NEUROSCIENCE 12 (2018): n. pag. Print.
@article{8598962,
  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.},
  articleno    = {389},
  author       = {Verstraelen, Peter and Van Dyck, Michiel and Verschuuren, Marlies and Kashikar, Nachiket D and Nuydens, Rony and Timmermans, Jean-Pierre and De Vos, Winnok},
  issn         = {1662-453X},
  journal      = {FRONTIERS IN NEUROSCIENCE},
  language     = {eng},
  pages        = {20},
  title        = {Image-based profiling of synaptic connectivity in primary neuronal cell culture},
  url          = {http://dx.doi.org/10.3389/fnins.2018.00389},
  volume       = {12},
  year         = {2018},
}

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