Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging

© 2021 Danielson et al. Neuronal synapses contain hundreds of different protein species important for regulating signal transmission. Characterizing differential expression profiles of proteins within synapses in distinct regions of the brain has revealed a high degree of synaptic diversity defined...

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Main Authors: Danielson, Eric, Perez de Arce, Karen, Cimini, Beth, Wamhoff, Eike-Christian, Singh, Shantanu, Cottrell, Jeffrey R, Carpenter, Anne E, Bathe, Mark
Format: Article
Language:English
Published: Society for Neuroscience 2021
Online Access:https://hdl.handle.net/1721.1/133122
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author Danielson, Eric
Perez de Arce, Karen
Cimini, Beth
Wamhoff, Eike-Christian
Singh, Shantanu
Cottrell, Jeffrey R
Carpenter, Anne E
Bathe, Mark
author_facet Danielson, Eric
Perez de Arce, Karen
Cimini, Beth
Wamhoff, Eike-Christian
Singh, Shantanu
Cottrell, Jeffrey R
Carpenter, Anne E
Bathe, Mark
author_sort Danielson, Eric
collection MIT
description © 2021 Danielson et al. Neuronal synapses contain hundreds of different protein species important for regulating signal transmission. Characterizing differential expression profiles of proteins within synapses in distinct regions of the brain has revealed a high degree of synaptic diversity defined by unique molecular organization. Multiplexed imaging of in vitro rat primary hippocampal culture models at single synapse resolution offers new opportunities for exploring synaptic reor-ganization in response to chemical and genetic perturbations. Here, we combine 12-color multiplexed fluorescence imaging with quantitative image analysis and machine learning to identify novel synaptic subtypes within excitatory and inhibitory synapses based on the expression profiles of major synaptic components. We characterize differences in the correlated expression of proteins within these subtypes and we examine how the distribution of these synapses is modified following induction of synaptic plasticity. Under chronic suppression of neuronal activity, phenotypic characterization revealed coordinated increases in both excitatory and inhibitory protein levels without changes in the distribution of synaptic subtypes, suggesting concerted events targeting glutamatergic and GABAergic synapses. Our results offer molecular insight into the mechanisms of synaptic plasticity.
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spelling mit-1721.1/1331222021-10-27T19:54:46Z Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging Danielson, Eric Perez de Arce, Karen Cimini, Beth Wamhoff, Eike-Christian Singh, Shantanu Cottrell, Jeffrey R Carpenter, Anne E Bathe, Mark © 2021 Danielson et al. Neuronal synapses contain hundreds of different protein species important for regulating signal transmission. Characterizing differential expression profiles of proteins within synapses in distinct regions of the brain has revealed a high degree of synaptic diversity defined by unique molecular organization. Multiplexed imaging of in vitro rat primary hippocampal culture models at single synapse resolution offers new opportunities for exploring synaptic reor-ganization in response to chemical and genetic perturbations. Here, we combine 12-color multiplexed fluorescence imaging with quantitative image analysis and machine learning to identify novel synaptic subtypes within excitatory and inhibitory synapses based on the expression profiles of major synaptic components. We characterize differences in the correlated expression of proteins within these subtypes and we examine how the distribution of these synapses is modified following induction of synaptic plasticity. Under chronic suppression of neuronal activity, phenotypic characterization revealed coordinated increases in both excitatory and inhibitory protein levels without changes in the distribution of synaptic subtypes, suggesting concerted events targeting glutamatergic and GABAergic synapses. Our results offer molecular insight into the mechanisms of synaptic plasticity. 2021-10-25T19:23:52Z 2021-10-25T19:23:52Z 2021 2021-08-24T18:39:12Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133122 Danielson, Eric, Perez de Arce, Karen, Cimini, Beth, Wamhoff, Eike-Christian, Singh, Shantanu et al. 2021. "Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging." eNeuro, 8 (1). en 10.1523/ENEURO.0286-20.2020 eNeuro Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Society for Neuroscience Society for Neuroscience
spellingShingle Danielson, Eric
Perez de Arce, Karen
Cimini, Beth
Wamhoff, Eike-Christian
Singh, Shantanu
Cottrell, Jeffrey R
Carpenter, Anne E
Bathe, Mark
Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging
title Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging
title_full Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging
title_fullStr Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging
title_full_unstemmed Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging
title_short Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging
title_sort molecular diversity of glutamatergic and gabaergic synapses from multiplexed fluorescence imaging
url https://hdl.handle.net/1721.1/133122
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