title: Modelling and Analysis of Electrical Potentials Recorded in Microelectrode Arrays (MEAs).
abstract: Microelectrode arrays (MEAs), substrate-integrated planar arrays of up to thousands of closely spaced metal electrode contacts, have long been used to record neuronal activity in in vitro brain slices with high spatial and temporal resolution. However, the analysis of the MEA potentials has generally been mainly qualitative. Here we use a biophysical forward-modelling formalism based on the finite element method (FEM) to establish quantitatively accurate links between neural activity in the slice and potentials recorded in the MEA set-up. Then we develop a simpler approach based on the method of images (MoI) from electrostatics, which allows for computation of MEA potentials by simple formulas similar to what is used for homogeneous volume conductors. As we find MoI to give accurate results in most situations of practical interest, including anisotropic slices covered with highly conductive saline and MEA-electrode contacts of sizable physical extensions, a Python software package (ViMEAPy) has been developed to facilitate forward-modelling of MEA potentials generated by biophysically detailed multicompartmental neurons. We apply our scheme to investigate the influence of the MEA set-up on single-neuron spikes as well as on potentials generated by a cortical network comprising more than 3000 model neurons. The generated MEA potentials are substantially affected by both the saline bath covering the brain slice and a (putative) inadvertent saline layer at the interface between the MEA chip and the brain slice. We further explore methods for estimation of current-source density (CSD) from MEA potentials, and find the results to be much less sensitive to the experimental set-up.
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Torbjørn V
authors.initials: TV
authors.lastname: Ness
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Chintaluri
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Potworowski
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Łęski
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Helena
authors.initials: H
authors.lastname: Głąbska
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Wójcik
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway. Gaute.Einevoll@nmbu.no.|Department of Physics, University of Oslo, Oslo, Norway. Gaute.Einevoll@nmbu.no.
authors.forename: Gaute T
authors.initials: GT
authors.lastname: Einevoll
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology; D006801:Humans; D008839:Microelectrodes; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000502:physiology*
keywords: Current source density; Finite element method; Method of images; Microelectrode array; Modelling
references.citation: PLoS Comput Biol. 2010 Dec 02;6(12):e1001013
references.pmid: 21152008
references.citation: Exp Brain Res. 2002 Jan;142(2):268-74
references.pmid: 11807580
references.citation: J Neurosci. 2012 Aug 22;32(34):11798-811
references.pmid: 22915121
references.citation: J Neurosci Methods. 2006 Sep 15;155(2):296-9
references.pmid: 16494949
references.citation: PLoS One. 2011;6(6):e20810
references.pmid: 21674067
references.citation: Nature. 2006 Apr 20;440(7087):1007-12
references.pmid: 16625187
references.citation: J Neurosci Methods. 2015 Apr 30;245:182-204
references.pmid: 25662445
references.citation: Ann Biomed Eng. 2001 Mar;29(3):227-35
references.pmid: 11310784
references.citation: J Neurosci Methods. 2002 Mar 15;114(2):135-48
references.pmid: 11856564
references.citation: PLoS One. 2009;4(3):e4828
references.pmid: 19279677
references.citation: J Neurophysiol. 2010 May;103(5):2315-7
references.pmid: 20220081
references.citation: Neuron. 2007 Sep 6;55(5):809-23
references.pmid: 17785187
references.citation: PLoS Comput Biol. 2013;9(7):e1003137
references.pmid: 23874180
references.citation: J Neurophysiol. 1968 Nov;31(6):884-915
references.pmid: 5710539
references.citation: Neuron. 2011 Dec 8;72(5):859-72
references.pmid: 22153380
references.citation: Front Neuroinform. 2014 Mar 19;8:26
references.pmid: 24678297
references.citation: J Neurosci Methods. 2012 Oct 15;211(1):133-44
references.pmid: 22960053
references.citation: PLoS One. 2014 Aug 25;9(8):e105071
references.pmid: 25153730
references.citation: Neuroinformatics. 2011 Dec;9(4):401-25
references.pmid: 21409556
references.citation: Curr Opin Neurobiol. 2012 Feb;22(1):11-7
references.pmid: 22023727
references.citation: Biosens Bioelectron. 2009 Mar 15;24(7):2191-8
references.pmid: 19157842
references.citation: J Neurosci. 2010 Dec 1;30(48):16332-42
references.pmid: 21123579
references.citation: J Neurophysiol. 2012 Sep;108(6):1793-803
references.pmid: 22745460
references.citation: Neuroscience. 2001;108(2):249-62
references.pmid: 11734358
references.citation: Front Cell Neurosci. 2013 Jun 07;7:88
references.pmid: 23761736
references.citation: J Physiol Paris. 2012 May-Aug;106(3-4):146-58
references.pmid: 22036892
references.citation: Nat Rev Neurosci. 2013 Nov;14(11):770-85
references.pmid: 24135696
references.citation: J Neurophysiol. 2006 Jun;95(6):3311-27
references.pmid: 16436479
references.citation: Neural Comput. 2013 May;25(5):1191-212
references.pmid: 23470125
references.citation: Nat Rev Neurosci. 2012 May 18;13(6):407-20
references.pmid: 22595786
references.citation: J Neurophysiol. 2005 Apr;93(4):2194-232
references.pmid: 15525801
references.citation: Biophys J. 1962 Mar;2(2 Pt 2):145-67
references.pmid: 14490040
references.citation: J Neurophysiol. 2007 Mar;97(3):2174-90
references.pmid: 17182911
references.citation: Nat Methods. 2010 Mar;7(3):200-2
references.pmid: 20118930
references.citation: J Neural Eng. 2008 Mar;5(1):54-67
references.pmid: 18310811
references.citation: Front Neural Circuits. 2012 Dec 20;6:105
references.pmid: 23267316
references.citation: J Comput Neurosci. 2010 Dec;29(3):423-44
references.pmid: 20502952
references.citation: J Comput Neurosci. 1999 Mar-Apr;6(2):169-84
references.pmid: 10333161
references.citation: J Comput Neurosci. 2012 Feb;32(1):73-100
references.pmid: 21667156
references.citation: Neuron. 2007 Apr 19;54(2):219-35
references.pmid: 17442244
references.citation: J Comput Neurosci. 2008 Jun;24(3):291-313
references.pmid: 17926125
references.citation: Neuron. 2013 Jul 24;79(2):375-90
references.pmid: 23889937
references.citation: J Neurophysiol. 2006 May;95(5):3113-28
references.pmid: 16467426
references.citation: Front Neuroinform. 2014 Jan 16;7:41
references.pmid: 24474916
references.citation: PLoS Comput Biol. 2011 Jul;7(7):e1002107
references.pmid: 21829333
references.citation: Exp Brain Res. 1987;67(2):402-10
references.pmid: 3622698
references.citation: J Neural Eng. 2013 Apr;10(2):026019
references.pmid: 23503026
references.citation: Nat Neurosci. 2004 Oct;7(10):1154-61
references.pmid: 15452581
references.citation: J Neurosci. 2011 Feb 9;31(6):2280-91
references.pmid: 21307264
references.citation: Neural Netw. 2009 Oct;22(8):1159-68
references.pmid: 19665350
references.citation: J Neurosci Methods. 2006 Jun 30;154(1-2):116-33
references.pmid: 16436298
references.citation: IEEE Trans Biomed Eng. 2008 Feb;55(2 Pt 1):683-92
references.pmid: 18270005
references.citation: Neural Comput. 1997 Aug 15;9(6):1179-209
references.pmid: 9248061
references.citation: J Comput Neurosci. 2007 Aug;23(1):39-58
references.pmid: 17273940
references.citation: PLoS One. 2013;8(3):e59839
references.pmid: 23555799
references.citation: Biophys J. 2008 Feb 1;94(3):784-802
references.pmid: 17921225
references.citation: J Neurophysiol. 2010 Dec;104(6):3388-412
references.pmid: 20810682
references.citation: Neural Comput. 2012 Feb;24(2):541-75
references.pmid: 22091662
references.citation: Clin Neurophysiol. 2005 Sep;116(9):2240-50
references.pmid: 16055377
references.citation: J Clin Neurophysiol. 2005 Oct;22(5):330-42
references.pmid: 16357637
references.citation: Neuroinformatics. 2007 Winter;5(4):207-22
references.pmid: 18040890
references.citation: J Neurophysiol. 1975 Mar;38(2):356-68
references.pmid: 805215