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 ne...
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| Published in: | Scientific reports Vol. 8; no. 1; pp. 10820 - 9 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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17-07-2018
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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. Abstract 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. |
| ArticleNumber | 10820 |
| Author | Enright, Heather A. Sales, Ana Paula Kuhn, Edward A. Belle, Anna M. Kulp, Kristen Wheeler, Elizabeth K. Osburn, Joanne Fischer, Nicholas O. |
| Author_xml | – sequence: 1 givenname: Anna M. surname: Belle fullname: Belle, Anna M. organization: Engineering Directorate, Lawrence Livermore National Laboratory, Livermore – sequence: 2 givenname: Heather A. orcidid: 0000-0001-6422-0481 surname: Enright fullname: Enright, Heather A. organization: Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore – sequence: 3 givenname: Ana Paula surname: Sales fullname: Sales, Ana Paula organization: Engineering Directorate, Lawrence Livermore National Laboratory, Livermore – sequence: 4 givenname: Kristen surname: Kulp fullname: Kulp, Kristen organization: Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore – sequence: 5 givenname: Joanne surname: Osburn fullname: Osburn, Joanne organization: Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore – sequence: 6 givenname: Edward A. surname: Kuhn fullname: Kuhn, Edward A. organization: Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore – sequence: 7 givenname: Nicholas O. surname: Fischer fullname: Fischer, Nicholas O. email: fischer29@llnl.gov organization: Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore – sequence: 8 givenname: Elizabeth K. surname: Wheeler fullname: Wheeler, Elizabeth K. email: wheeler16@llnl.gov organization: Engineering Directorate, Lawrence Livermore National Laboratory, Livermore |
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| Snippet | Quantitatively benchmarking similarities and differences between the
in vivo
central nervous system and
in vitro
neuronal cultures can qualify discrepancies in... Quantitatively benchmarking similarities and differences between the in vivo central nervous system and in vitro neuronal cultures can qualify discrepancies in... Abstract Quantitatively benchmarking similarities and differences between the in vivo central nervous system and in vitro neuronal cultures can qualify... |
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| Title | Evaluation of in vitro neuronal platforms as surrogates for in vivo whole brain systems |
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