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

Belle, Anna M.; Enright, Heather A.; Sales, Ana Paula; Kulp, Kristen; Osburn, Joanne; Kuhn, Edward A.; Fischer, Nicholas O.; Wheeler, Elizabeth K.

doi:10.1038/s41598-018-28950-5

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

Journal Article · 17 July 2018 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-018-28950-5 · OSTI ID:1459734

Belle, Anna M.;

; Sales, Ana Paula; Kulp, Kristen; Osburn, Joanne; Kuhn, Edward A.; Fischer, Nicholas O.; Wheeler, Elizabeth K.

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.

View Journal Article

Cite

Export

Save

Sponsoring Organization:: USDOE

OSTI ID:: 1459734

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 8; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (54)

The glia/neuron ratio: How it varies uniformly across brain structures and species and what that means for brain physiology and evolution: The Glia/Neuron Ratio Herculano-Houzel, Suzana Glia, Vol. 62, Issue 9 https://doi.org/10.1002/glia.22683	journal	May 2014
The distribution and clearance of (2S,6S)-hydroxynorketamine, an active ketamine metabolite, in Wistar rats Moaddel, Ruin; Sanghvi, Mitesh; Dossou, Katina Sourou Sylvestre Pharmacology Research & Perspectives, Vol. 3, Issue 4 https://doi.org/10.1002/prp2.157	journal	June 2015
Muscarinic agonists modulate spontaneous and evoked unit discharge in auditory cortex of cat McKenna, Thomas M.; Ashe, John H.; Hui, Gabriel K. Synapse, Vol. 2, Issue 1 https://doi.org/10.1002/syn.890020109	journal	January 1988
Quantitative analysis of neurons and glial cells in the rat somatosensory cortex, with special reference to GABAergic neurons and parvalbumin-containing neurons Ren, J. Q.; Aika, Y.; Heizmann, C. W. Experimental Brain Research, Vol. 92, Issue 1 https://doi.org/10.1007/BF00230378	journal	December 1992
The subpopulation of microglia expressing functional muscarinic acetylcholine receptors expands in stroke and Alzheimer’s disease Pannell, Maria; Meier, Maria Almut; Szulzewsky, Frank Brain Structure and Function, Vol. 221, Issue 2 https://doi.org/10.1007/s00429-014-0962-y	journal	December 2014
The Effects of Acute GABA Treatment on the Functional Connectivity and Network Topology of Cortical Cultures Han, Yao; Li, Hong; Lang, Yiran Neurochemical Research, Vol. 42, Issue 5 https://doi.org/10.1007/s11064-017-2190-3	journal	March 2017
Rat hippocampal neurons in dispersed cell culture Banker, Gary A.; Cowan, W. Maxwell Brain Research, Vol. 126, Issue 3 https://doi.org/10.1016/0006-8993(77)90594-7	journal	May 1977
Distribution of 3H-methylatropine in rat brain Witter, A.; Slangen, J. L.; Terpstra, G. K. Neuropharmacology, Vol. 12, Issue 9 https://doi.org/10.1016/0028-3908(73)90036-1	journal	September 1973
Distribution of muscarinic receptor subtypes in rat brain from postnatal to old age Tice, Melissa A. B.; Hashemi, Tanaz; Taylor, Lisa A. Developmental Brain Research, Vol. 92, Issue 1 https://doi.org/10.1016/0165-3806(95)01515-9	journal	March 1996
Mechanical and enzymatic isolation of mammalian CNS neurons Kaneda, Makoto; Nakamura, Hiroyuki; Akaike, Norio Neuroscience Research, Vol. 5, Issue 4 https://doi.org/10.1016/0168-0102(88)90032-6	journal	April 1988
Isolation and culture of adult rat hippocampal neurons Brewer, Gregory J. Journal of Neuroscience Methods, Vol. 71, Issue 2 https://doi.org/10.1016/S0165-0270(96)00136-7	journal	February 1997
Electrophysiology of embryonic, adult and aged rat hippocampal neurons in serum-free culture Evans, M. Steven; Collings, Melissa A.; Brewer, Gregory J. Journal of Neuroscience Methods, Vol. 79, Issue 1 https://doi.org/10.1016/S0165-0270(97)00159-3	journal	January 1998
Animal models of human disease: Challenges in enabling translation McGonigle, Paul; Ruggeri, Bruce Biochemical Pharmacology, Vol. 87, Issue 1 https://doi.org/10.1016/j.bcp.2013.08.006	journal	January 2014
Dissociated cortical networks show spontaneously correlated activity patterns during in vitro development Chiappalone, Michela; Bove, Marco; Vato, Alessandro Brain Research, Vol. 1093, Issue 1 https://doi.org/10.1016/j.brainres.2006.03.049	journal	June 2006
Prefrontal cortex and drug abuse vulnerability: Translation to prevention and treatment interventions Perry, Jennifer L.; Joseph, Jane E.; Jiang, Yang Brain Research Reviews, Vol. 65, Issue 2 https://doi.org/10.1016/j.brainresrev.2010.09.001	journal	January 2011
Sublime Microglia: Expanding Roles for the Guardians of the CNS Salter, Michael W.; Beggs, Simon Cell, Vol. 158, Issue 1 https://doi.org/10.1016/j.cell.2014.06.008	journal	July 2014
Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations Langley, Gillian R.; Adcock, Ian M.; Busquet, François Drug Discovery Today, Vol. 22, Issue 2 https://doi.org/10.1016/j.drudis.2016.10.011	journal	February 2017
Optimized protocols for the simultaneous preparation of primary neuronal cultures of the neocortex, hippocampus and cerebellum from individual newborn (P0.5) C57Bl/6J mice Ahlemeyer, Barbara; Baumgart-Vogt, Eveline Journal of Neuroscience Methods, Vol. 149, Issue 2 https://doi.org/10.1016/j.jneumeth.2005.05.022	journal	December 2005
Neuronal-glial populations form functional networks in a biocompatible 3D scaffold Smith, Imogen; Haag, Marcus; Ugbode, Christopher Neuroscience Letters, Vol. 609 https://doi.org/10.1016/j.neulet.2015.10.044	journal	November 2015
A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays Wallace, Kathleen; Strickland, Jenna D.; Valdivia, Pablo NeuroToxicology, Vol. 49 https://doi.org/10.1016/j.neuro.2015.05.007	journal	July 2015
Brain maturation of the adolescent rat cortex and striatum: Changes in volume and myelination Mengler, Luam; Khmelinskii, Artem; Diedenhofen, Michael NeuroImage, Vol. 84 https://doi.org/10.1016/j.neuroimage.2013.08.034	journal	January 2014
A Role for Correlated Spontaneous Activity in the Assembly of Neural Circuits Kirkby, Lowry A.; Sack, Georgeann S.; Firl, Alana Neuron, Vol. 80, Issue 5 https://doi.org/10.1016/j.neuron.2013.10.030	journal	December 2013
Do in vitro assays in rat primary neurons predict drug-induced seizure liability in humans? Kreir, M.; Van Deuren, B.; Versweyveld, S. Toxicology and Applied Pharmacology, Vol. 346 https://doi.org/10.1016/j.taap.2018.03.028	journal	May 2018
Classics in Chemical Neuroscience: Ketamine Tyler, Marshall W.; Yourish, Harmony B.; Ionescu, Dawn F. ACS Chemical Neuroscience, Vol. 8, Issue 6 https://doi.org/10.1021/acschemneuro.7b00074	journal	April 2017
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Zanos, Panos; Moaddel, Ruin; Morris, Patrick J. Nature, Vol. 533, Issue 7604 https://doi.org/10.1038/nature17998	journal	May 2016
Effects of a ketamine metabolite on synaptic NMDAR function Suzuki, Kanzo; Nosyreva, Elena; Hunt, Kevin W. Nature, Vol. 546, Issue 7659 https://doi.org/10.1038/nature22084	journal	June 2017
Behavior-dependent short-term assembly dynamics in the medial prefrontal cortex Fujisawa, Shigeyoshi; Amarasingham, Asohan; Harrison, Matthew T. Nature Neuroscience, Vol. 11, Issue 7 https://doi.org/10.1038/nn.2134	journal	May 2008
Isolation and culture of adult neurons and neurospheres Brewer, Gregory J.; Torricelli, John R. Nature Protocols, Vol. 2, Issue 6 https://doi.org/10.1038/nprot.2007.207	journal	June 2007
Screening out irrelevant cell-based models of disease Horvath, Peter; Aulner, Nathalie; Bickle, Marc Nature Reviews Drug Discovery, Vol. 15, Issue 11 https://doi.org/10.1038/nrd.2016.175	journal	September 2016
Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia Roth, Bryan L.; Sheffler, Douglas J.; Kroeze, Wesley K. Nature Reviews Drug Discovery, Vol. 3, Issue 4 https://doi.org/10.1038/nrd1346	journal	April 2004
Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications Goldstein, Rita Z.; Volkow, Nora D. Nature Reviews Neuroscience, Vol. 12, Issue 11 https://doi.org/10.1038/nrn3119	journal	October 2011
Emerging roles of astrocytes in neural circuit development Clarke, Laura E.; Barres, Ben A. Nature Reviews Neuroscience, Vol. 14, Issue 5 https://doi.org/10.1038/nrn3484	journal	April 2013
Regulation of muscarinic receptor function in developing oligodendrocytes by agonist exposure Molina-Holgado, Eduardo; Khorchid, Amani; Liu, Hsueh-Ning British Journal of Pharmacology, Vol. 138, Issue 1 https://doi.org/10.1038/sj.bjp.0705002	journal	January 2003
Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology Shapiro, David A.; Renock, Sean; Arrington, Elaine Neuropsychopharmacology, Vol. 28, Issue 8 https://doi.org/10.1038/sj.npp.1300203	journal	March 2003
Long-term non-invasive interrogation of human dorsal root ganglion neuronal cultures on an integrated microfluidic multielectrode array platform Enright, H. A.; Felix, S. H.; Fischer, N. O. The Analyst, Vol. 141, Issue 18 https://doi.org/10.1039/C5AN01728A	journal	January 2016
NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex Jackson, M. E.; Homayoun, H.; Moghaddam, B. Proceedings of the National Academy of Sciences, Vol. 101, Issue 22 https://doi.org/10.1073/pnas.0308455101	journal	May 2004
Metabolism and metabolomics of ketamine: a toxicological approach Dinis-Oliveira, Ricardo Jorge Forensic Sciences Research, Vol. 2, Issue 1 https://doi.org/10.1080/20961790.2017.1285219	journal	January 2017
Enhanced Coupling of Neonatal Muscarinic Receptors in Rat Brain to Phosphoinositide Turnover Heacock, Anne M.; Fisher, Stephen K.; Agranoff, Bernard W. Journal of Neurochemistry, Vol. 48, Issue 6 https://doi.org/10.1111/j.1471-4159.1987.tb05754.x	journal	June 1987
Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain Ikonomidou, C. Science, Vol. 283, Issue 5398 https://doi.org/10.1126/science.283.5398.70	journal	January 1999
Glycine Tranporter-1 Blockade Potentiates NMDA-Mediated Responses in Rat Prefrontal Cortical Neurons In Vitro and In Vivo Chen, Long; Muhlhauser, Mark; Yang, Charles R. Journal of Neurophysiology, Vol. 89, Issue 2 https://doi.org/10.1152/jn.00680.2002	journal	February 2003
NMDA Receptors in Glia Verkhratsky, Alexei; Kirchhoff, Frank The Neuroscientist, Vol. 13, Issue 1 https://doi.org/10.1177/1073858406294270	journal	February 2007
Three-Dimensional Cell Cultures in Drug Discovery and Development Fang, Ye; Eglen, Richard M. SLAS DISCOVERY: Advancing Life Sciences R&D, Vol. 22, Issue 5 https://doi.org/10.1177/1087057117696795	journal	May 2017
Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures Charlesworth, Paul; Cotterill, Ellese; Morton, Andrew Neural Development, Vol. 10, Issue 1 https://doi.org/10.1186/s13064-014-0028-0	journal	January 2015
Ketamine Effects on Somatosensory Cortical Single Neurons and on Behavior in Rats Patel, Ishvarlal M.; Chapin, John K. Anesthesia & Analgesia, Vol. 70, Issue 6 https://doi.org/10.1213/00000539-199006000-00010	journal	January 1990
Controlled placement of multiple CNS cell populations to create complex neuronal cultures Soscia, D.; Belle, A.; Fischer, N. PLOS ONE, Vol. 12, Issue 11 https://doi.org/10.1371/journal.pone.0188146	journal	November 2017
Glutamate neurotoxicity in cortical cell culture Choi, Dw; Maulucci-Gedde, M.; Kriegstein, Ar The Journal of Neuroscience, Vol. 7, Issue 2 https://doi.org/10.1523/JNEUROSCI.07-02-00357.1987	journal	February 1987
Ketamine: NMDA Receptors and Beyond Zorumski, Charles F.; Izumi, Yukitoshi; Mennerick, Steven The Journal of Neuroscience, Vol. 36, Issue 44 https://doi.org/10.1523/JNEUROSCI.1547-16.2016	journal	November 2016
NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons Homayoun, H.; Moghaddam, B. Journal of Neuroscience, Vol. 27, Issue 43 https://doi.org/10.1523/JNEUROSCI.2213-07.2007	journal	October 2007
The Fraction of Cortical GABAergic Neurons Is Constant from Near the Start of Cortical Neurogenesis to Adulthood Sahara, S.; Yanagawa, Y.; O'Leary, D. D. M. Journal of Neuroscience, Vol. 32, Issue 14 https://doi.org/10.1523/JNEUROSCI.6412-11.2012	journal	April 2012
Metabolic Aspects of Neuron-Oligodendrocyte-Astrocyte Interactions Amaral, Ana I.; Meisingset, Tore W.; Kotter, Mark R. Frontiers in Endocrinology, Vol. 4 https://doi.org/10.3389/fendo.2013.00054	journal	January 2013
Development of Micro-Electrode Array Based Tests for Neurotoxicity: Assessment of Interlaboratory Reproducibility with Neuroactive Chemicals Novellino, A.; Scelfo, Bibiana; Palosaari, T. Frontiers in Neuroengineering, Vol. 4 https://doi.org/10.3389/fneng.2011.00004	journal	January 2011
Distribution and effects of the muscarinic receptor subtypes in the primary visual cortex Groleau, Marianne; Kang, Jun Il; Huppé-Gourgues, Frédéric Frontiers in Synaptic Neuroscience, Vol. 7 https://doi.org/10.3389/fnsyn.2015.00010	journal	June 2015
Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning Langhans, Sigrid A. Frontiers in Pharmacology, Vol. 9 https://doi.org/10.3389/fphar.2018.00006	journal	January 2018
Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive Felix, Sarah H.; Shah, Kedar G.; Tolosa, Vanessa M. Journal of Visualized Experiments, Issue 79 https://doi.org/10.3791/50609	journal	January 2013

Similar Records

Long-term non-invasive interrogation of human dorsal root ganglion neuronal cultures on an integrated microfluidic multielectrode array platform

Journal Article · 2016 · Analyst · OSTI ID:1467804

Enright, H. A.; Felix, S. H.; Fischer, N. O.; +10 more

Assessment of primary neuronal culture as a model for soman-induced neurotoxicity and effectiveness of nemantine as a neuroprotective drug

Technical Report · 1995 · OSTI ID:220279

Deshpande, S S; Smith, C D; Filbert, M G

Assessment of primary neuronal culture as a model for soman-induced neurotoxicity and effectiveness of memantine as a neuroprotective drug

Technical Report · 1995 · OSTI ID:220278

Deshpande, S S; Smith, C D; Filbert, M G

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

Citation Formats

References (54)

Similar Records

Related Subjects