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Title: Tissue-specific extracellular matrix accelerates the formation of neural networks and communities in a neuron-glia co-culture on a multi-electrode array

Abstract

The brain’s extracellular matrix (ECM) is a macromolecular network composed of glycosaminoglycans, proteoglycans, glycoproteins, and fibrous proteins. In vitro studies often use purified ECM proteins for cell culture coatings, however these may not represent the molecular complexity and heterogeneity of the brain’s ECM. To address this, we compared neural network activity (over 30 days in vitro) from primary neurons co-cultured with glia grown on ECM coatings from decellularized brain tissue (bECM) or MaxGel, a non-tissue-specific ECM. Cells were grown on a multi-electrode array (MEA) to enable noninvasive long-term interrogation of neuronal networks. In general, the presence of ECM accelerated the formation of networks without affecting the inherent network properties. However, specific features of network activity were dependent on the type of ECM: bECM enhanced network activity over a greater region of the MEA whereas MaxGel increased network burst rate associated with robust synaptophysin expression. These differences in network activity were not attributable to cellular composition, glial proliferation, or astrocyte phenotypes, which remained constant across experimental conditions. Collectively, the addition of ECM to neuronal cultures represents a reliable method to accelerate the development of mature neuronal networks, providing a means to enhance throughput for routine evaluation of neurotoxins and novel therapeutics.

Authors:
ORCiD logo [1]; ORCiD logo [1];  [2];  [1];  [2];  [1];  [2];  [1];  [2];  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences Directorate
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Engineering Directorate
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE; LLNL Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1513163
Report Number(s):
LLNL-JRNL-758714
Journal ID: ISSN 2045-2322; 947059
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 9; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cellular neuroscience; neural circuits

Citation Formats

Lam, Doris, Enright, Heather A., Cadena, Jose, Peters, Sandra K. G., Sales, Ana Paula, Osburn, Joanne J., Soscia, David A., Kulp, Kristen S., Wheeler, Elizabeth K., and Fischer, Nicholas O. Tissue-specific extracellular matrix accelerates the formation of neural networks and communities in a neuron-glia co-culture on a multi-electrode array. United States: N. p., 2019. Web. doi:10.1038/s41598-019-40128-1.
Lam, Doris, Enright, Heather A., Cadena, Jose, Peters, Sandra K. G., Sales, Ana Paula, Osburn, Joanne J., Soscia, David A., Kulp, Kristen S., Wheeler, Elizabeth K., & Fischer, Nicholas O. Tissue-specific extracellular matrix accelerates the formation of neural networks and communities in a neuron-glia co-culture on a multi-electrode array. United States. doi:10.1038/s41598-019-40128-1.
Lam, Doris, Enright, Heather A., Cadena, Jose, Peters, Sandra K. G., Sales, Ana Paula, Osburn, Joanne J., Soscia, David A., Kulp, Kristen S., Wheeler, Elizabeth K., and Fischer, Nicholas O. Mon . "Tissue-specific extracellular matrix accelerates the formation of neural networks and communities in a neuron-glia co-culture on a multi-electrode array". United States. doi:10.1038/s41598-019-40128-1. https://www.osti.gov/servlets/purl/1513163.
@article{osti_1513163,
title = {Tissue-specific extracellular matrix accelerates the formation of neural networks and communities in a neuron-glia co-culture on a multi-electrode array},
author = {Lam, Doris and Enright, Heather A. and Cadena, Jose and Peters, Sandra K. G. and Sales, Ana Paula and Osburn, Joanne J. and Soscia, David A. and Kulp, Kristen S. and Wheeler, Elizabeth K. and Fischer, Nicholas O.},
abstractNote = {The brain’s extracellular matrix (ECM) is a macromolecular network composed of glycosaminoglycans, proteoglycans, glycoproteins, and fibrous proteins. In vitro studies often use purified ECM proteins for cell culture coatings, however these may not represent the molecular complexity and heterogeneity of the brain’s ECM. To address this, we compared neural network activity (over 30 days in vitro) from primary neurons co-cultured with glia grown on ECM coatings from decellularized brain tissue (bECM) or MaxGel, a non-tissue-specific ECM. Cells were grown on a multi-electrode array (MEA) to enable noninvasive long-term interrogation of neuronal networks. In general, the presence of ECM accelerated the formation of networks without affecting the inherent network properties. However, specific features of network activity were dependent on the type of ECM: bECM enhanced network activity over a greater region of the MEA whereas MaxGel increased network burst rate associated with robust synaptophysin expression. These differences in network activity were not attributable to cellular composition, glial proliferation, or astrocyte phenotypes, which remained constant across experimental conditions. Collectively, the addition of ECM to neuronal cultures represents a reliable method to accelerate the development of mature neuronal networks, providing a means to enhance throughput for routine evaluation of neurotoxins and novel therapeutics.},
doi = {10.1038/s41598-019-40128-1},
journal = {Scientific Reports},
number = ,
volume = 9,
place = {United States},
year = {2019},
month = {3}
}

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    Works referencing / citing this record:

    Mechanotransduction in neuronal cell development and functioning
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