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 »
- Authors:
-
[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}
}