Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons

Abstract During acute neuroinflammation, increased levels of cytokines within the brain may contribute to synaptic reorganization that results in long-term changes in network hyperexcitability. Indeed, inflammatory cytokines are implicated in synaptic dysfunction in epilepsy and in an array of degen...

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Autores principales:	Benjamin D. S. Clarkson, Robert J. Kahoud, Christina B. McCarthy, Charles L. Howe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e0ef023671b49c3bc9fbae98d663724
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spelling	oai:doaj.org-article:0e0ef023671b49c3bc9fbae98d6637242021-12-02T11:52:28ZInflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons10.1038/s41598-017-09182-52045-2322https://doaj.org/article/0e0ef023671b49c3bc9fbae98d6637242017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09182-5https://doaj.org/toc/2045-2322Abstract During acute neuroinflammation, increased levels of cytokines within the brain may contribute to synaptic reorganization that results in long-term changes in network hyperexcitability. Indeed, inflammatory cytokines are implicated in synaptic dysfunction in epilepsy and in an array of degenerative and autoimmune diseases of the central nervous system. Current tools for studying the impact of inflammatory factors on neural networks are either insufficiently fast and sensitive or require complicated and costly experimental rigs. Calcium imaging offers a reasonable surrogate for direct measurement of neuronal network activity, but traditional imaging paradigms are confounded by cellular heterogeneity and cannot readily distinguish between glial and neuronal calcium transients. While the establishment of pure neuron cultures is possible, the removal of glial cells ignores physiologically relevant cell-cell interactions that may be critical for circuit level disruptions induced by inflammatory factors. To overcome these issues, we provide techniques and algorithms for image processing and waveform feature extraction using automated analysis of spontaneous and evoked calcium transients in primary murine cortical neuron cultures transduced with an adeno-associated viral vector driving the GCaMP6f reporter behind a synapsin promoter. Using this system, we provide evidence of network perturbations induced by the inflammatory cytokines TNFα, IL1β, and IFNγ.Benjamin D. S. ClarksonRobert J. KahoudChristina B. McCarthyCharles L. HoweNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin D. S. Clarkson Robert J. Kahoud Christina B. McCarthy Charles L. Howe Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons
description	Abstract During acute neuroinflammation, increased levels of cytokines within the brain may contribute to synaptic reorganization that results in long-term changes in network hyperexcitability. Indeed, inflammatory cytokines are implicated in synaptic dysfunction in epilepsy and in an array of degenerative and autoimmune diseases of the central nervous system. Current tools for studying the impact of inflammatory factors on neural networks are either insufficiently fast and sensitive or require complicated and costly experimental rigs. Calcium imaging offers a reasonable surrogate for direct measurement of neuronal network activity, but traditional imaging paradigms are confounded by cellular heterogeneity and cannot readily distinguish between glial and neuronal calcium transients. While the establishment of pure neuron cultures is possible, the removal of glial cells ignores physiologically relevant cell-cell interactions that may be critical for circuit level disruptions induced by inflammatory factors. To overcome these issues, we provide techniques and algorithms for image processing and waveform feature extraction using automated analysis of spontaneous and evoked calcium transients in primary murine cortical neuron cultures transduced with an adeno-associated viral vector driving the GCaMP6f reporter behind a synapsin promoter. Using this system, we provide evidence of network perturbations induced by the inflammatory cytokines TNFα, IL1β, and IFNγ.
format	article
author	Benjamin D. S. Clarkson Robert J. Kahoud Christina B. McCarthy Charles L. Howe
author_facet	Benjamin D. S. Clarkson Robert J. Kahoud Christina B. McCarthy Charles L. Howe
author_sort	Benjamin D. S. Clarkson
title	Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons
title_short	Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons
title_full	Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons
title_fullStr	Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons
title_full_unstemmed	Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons
title_sort	inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0e0ef023671b49c3bc9fbae98d663724
work_keys_str_mv	AT benjamindsclarkson inflammatorycytokineinducedchangesinneuralnetworkactivitymeasuredbywaveformanalysisofhighcontentcalciumimaginginmurinecorticalneurons AT robertjkahoud inflammatorycytokineinducedchangesinneuralnetworkactivitymeasuredbywaveformanalysisofhighcontentcalciumimaginginmurinecorticalneurons AT christinabmccarthy inflammatorycytokineinducedchangesinneuralnetworkactivitymeasuredbywaveformanalysisofhighcontentcalciumimaginginmurinecorticalneurons AT charleslhowe inflammatorycytokineinducedchangesinneuralnetworkactivitymeasuredbywaveformanalysisofhighcontentcalciumimaginginmurinecorticalneurons
_version_	1718395029910716416

Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons

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