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Title: Evaluation of in vitro neuronal platforms as surrogates for in vivo whole brain systems

Quantitatively benchmarking similarities and differences between the in vivo central nervous system and in vitro neuronal cultures can qualify discrepancies in functional responses and establish the utility of in vitro platforms. In this work, extracellular electrophysiology responses of cortical neurons in awake, freely-moving animals were compared to in vitro cultures of dissociated cortical neurons. After exposure to two well-characterized drugs, atropine and ketamine, a number of key points were observed: 1) significant differences in spontaneous firing activity for in vivo and in vitro systems, 2) similar response trends in single unit spiking activity after exposure to atropine, and 3) greater sensitivity to the effects of ketamine in vitro. While in vitro cultures of dissociated cortical neurons may be appropriate for many types of pharmacological studies, we demonstrate that for some drugs, such as ketamine, this system may not fully capture the responses observed in vivo. Understanding the functionality associated with neuronal cultures will enhance the relevance of electrophysiology data sets and more accurately frame their conclusions. Comparing in vivo and in vitro rodent systems will provide the critical framework necessary for developing and interpreting in vitro systems using human cells that strive to more closely recapitulate human in vivo functionmore » and response.« less
Authors:
 [1] ; ORCiD logo [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Publication Date:
Report Number(s):
LLNL-JRNL-746078
Journal ID: ISSN 2045-2322; 930334
Grant/Contract Number:
AC52-07NA27344
Type:
Published Article
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org:
USDOE National Nuclear Security Administration (NNSA)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1459734
Alternate Identifier(s):
OSTI ID: 1467806

Belle, Anna M., Enright, Heather A., Sales, Ana Paula, Kulp, Kristen, Osburn, Joanne, Kuhn, Edward A., Fischer, Nicholas O., and Wheeler, Elizabeth K.. Evaluation of in vitro neuronal platforms as surrogates for in vivo whole brain systems. United States: N. p., Web. doi:10.1038/s41598-018-28950-5.
Belle, Anna M., Enright, Heather A., Sales, Ana Paula, Kulp, Kristen, Osburn, Joanne, Kuhn, Edward A., Fischer, Nicholas O., & Wheeler, Elizabeth K.. Evaluation of in vitro neuronal platforms as surrogates for in vivo whole brain systems. United States. doi:10.1038/s41598-018-28950-5.
Belle, Anna M., Enright, Heather A., Sales, Ana Paula, Kulp, Kristen, Osburn, Joanne, Kuhn, Edward A., Fischer, Nicholas O., and Wheeler, Elizabeth K.. 2018. "Evaluation of in vitro neuronal platforms as surrogates for in vivo whole brain systems". United States. doi:10.1038/s41598-018-28950-5.
@article{osti_1459734,
title = {Evaluation of in vitro neuronal platforms as surrogates for in vivo whole brain systems},
author = {Belle, Anna M. and Enright, Heather A. and Sales, Ana Paula and Kulp, Kristen and Osburn, Joanne and Kuhn, Edward A. and Fischer, Nicholas O. and Wheeler, Elizabeth K.},
abstractNote = {Quantitatively benchmarking similarities and differences between the in vivo central nervous system and in vitro neuronal cultures can qualify discrepancies in functional responses and establish the utility of in vitro platforms. In this work, extracellular electrophysiology responses of cortical neurons in awake, freely-moving animals were compared to in vitro cultures of dissociated cortical neurons. After exposure to two well-characterized drugs, atropine and ketamine, a number of key points were observed: 1) significant differences in spontaneous firing activity for in vivo and in vitro systems, 2) similar response trends in single unit spiking activity after exposure to atropine, and 3) greater sensitivity to the effects of ketamine in vitro. While in vitro cultures of dissociated cortical neurons may be appropriate for many types of pharmacological studies, we demonstrate that for some drugs, such as ketamine, this system may not fully capture the responses observed in vivo. Understanding the functionality associated with neuronal cultures will enhance the relevance of electrophysiology data sets and more accurately frame their conclusions. Comparing in vivo and in vitro rodent systems will provide the critical framework necessary for developing and interpreting in vitro systems using human cells that strive to more closely recapitulate human in vivo function and response.},
doi = {10.1038/s41598-018-28950-5},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {2018},
month = {7}
}