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

• Published in: Scientific reports Vol. 8; no. 1; pp. 10820 - 9
• Main Authors: Belle, Anna M., Enright, Heather A., Sales, Ana Paula, Kulp, Kristen, Osburn, Joanne, Kuhn, Edward A., Fischer, Nicholas O., Wheeler, Elizabeth K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-07-2018; Nature Publishing Group
• Subjects: 13/106; 631/154/1435; 631/154/570; 631/378; 692/308/153; 9/10; Atropine; BASIC BIOLOGICAL SCIENCES; Central nervous system; Drug dosages; Electrophysiology; Firing pattern; Humanities and Social Sciences; Ketamine; Laboratories; Metabolites; multidisciplinary; Neurons; Science; Science (multidisciplinary); Trends
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-28950-5

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.