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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.

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