title: Caged neuron MEA: a system for long-term investigation of cultured neural network connectivity.
abstract: Traditional techniques for investigating cultured neural networks, such as the patch clamp and multi-electrode array, are limited by: (1) the number of identified cells which can be simultaneously electrically contacted, (2) the length of time for which cells can be studied, and (3) the lack of one-to-one neuron-to-electrode specificity. Here, we present a new device - the caged neuron multi-electrode array - which overcomes these limitations. This micro-machined device consists of an array of neurocages which mechanically trap a neuron near an extracellular electrode. While the cell body is trapped, the axon and dendrites can freely grow into the surrounding area to form a network. The electrode is bi-directional, capable of both stimulating and recording action potentials. This system is non-invasive, so that all constituent neurons of a network can be studied over its lifetime with stable one-to-one neuron-to-electrode correspondence. Proof-of-concept experiments are described to illustrate that functional networks form in a neurochip system of 16 cages in a 4 x 4 array, and that suprathreshold connectivity can be fully mapped over several weeks. The neurochip opens a new domain in neurobiology for studying small cultured neural networks.
authors.affiliation: Department of Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA. jonathan.erickson@vanderbilt.edu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Erickson
authors.forename: Angela
authors.initials: A
authors.lastname: Tooker
authors.forename: Y-C
authors.initials: YC
authors.lastname: Tai
authors.forename: Jerome
authors.initials: J
authors.lastname: Pine
mesh_terms: D000200:Action Potentials / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002470:Cell Survival; D002478:Cells, Cultured / Q000502:physiology; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods; D004566:Electrodes; D004594:Electrophysiology / Q000295:instrumentation* / Q000379:methods; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D008838:Microcomputers; D008855:Microscopy, Electron, Scanning; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D012825:Silicon
chemical_list: D012825:Silicon
references.citation: Brain Res Dev Brain Res. 1992 Oct 23;69(2):191-7
references.pmid: 1424096
references.citation: J Neurosci. 2001 Nov 15;21(22):8782-8
references.pmid: 11698590
references.citation: Nature. 1999 Oct 21;401(6755):792-6
references.pmid: 10548104
references.citation: Science. 2006 Aug 25;313(5790):1100-4
references.pmid: 16931757
references.citation: Nature. 2004 Oct 14;431(7010):789-95
references.pmid: 15483600
references.citation: J Physiol. 2005 Apr 1;564(Pt 1):3-19
references.pmid: 15618268
references.citation: J Neurosci Methods. 2002 May 30;117(1):13-21
references.pmid: 12084560
references.citation: Brain Res Bull. 1991 Mar;26(3):333-8
references.pmid: 2049599
references.citation: J Neurosci Res. 1993 Aug 1;35(5):567-76
references.pmid: 8377226
references.citation: J Neurosci. 2003 Oct 15;23(28):9349-56
references.pmid: 14561862
references.citation: Annu Rev Neurosci. 2001;24:139-66
references.pmid: 11283308
references.citation: Nat Neurosci. 2001 Nov;4 Suppl:1207-14
references.pmid: 11687831
references.citation: J Neurophysiol. 1997 Aug;78(2):1082-95
references.pmid: 9307136
references.citation: Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8918-21
references.pmid: 9238078
references.citation: J Neurosci Methods. 1980 Feb;2(1):19-31
references.pmid: 7329089
references.citation: J Neurophysiol. 1992 Mar;67(3):508-29
references.pmid: 1578242
references.citation: J Neurosci Methods. 2002 Oct 30;120(2):113-20
references.pmid: 12385761
references.citation: J Neurosci Methods. 1991 Jul;38(2-3):93-105
references.pmid: 1784131
references.citation: Conf Proc IEEE Eng Med Biol Soc. 2004;2004:2542-5
references.pmid: 17270791
references.citation: Neuron. 2000 Nov;28(2):559-69
references.pmid: 11144364
references.citation: IEEE Trans Biomed Eng. 2000 Mar;47(3):290-300
references.pmid: 10743770
references.citation: J Neurosci Methods. 2007 Mar 15;160(2):317-26
references.pmid: 17049614
references.citation: Nat Neurosci. 2002 Nov;5(11):1177-84
references.pmid: 12368805
references.citation: J Neurosci Methods. 2002 Jun 30;117(2):123-31
references.pmid: 12100977
references.citation: Biophys J. 1991 Sep;60(3):697-711
references.pmid: 1681956
references.citation: Biophys J. 1962 Mar;2(2 Pt 2):145-67
references.pmid: 14490040
references.citation: Nat Neurosci. 2004 Apr;7(4):327-32
references.pmid: 15048120
references.citation: Neurosci Lett. 1997 Feb 14;223(1):9-12
references.pmid: 9058410
references.citation: Curr Opin Neurobiol. 2001 Oct;11(5):536-43
references.pmid: 11595485
references.citation: Nature. 2004 Oct 14;431(7010):782-8
references.pmid: 15483599
references.citation: Nat Rev Neurosci. 2001 Jan;2(1):24-32
references.pmid: 11253356
references.citation: J Neurosci Methods. 1999 Feb 1;87(1):45-56
references.pmid: 10065993
references.citation: J Comput Neurosci. 1999 Mar-Apr;6(2):169-84
references.pmid: 10333161
references.citation: Cell Mol Life Sci. 1999 Aug 30;55(11):1448-62
references.pmid: 10518992
references.citation: Nature. 1997 Jul 31;388(6641):439-48
references.pmid: 9242402
references.citation: J Neurosci. 1998 Sep 15;18(18):7256-71
references.pmid: 9736647
references.citation: Neurosci Lett. 1977 Nov;6(2-3):101-5
references.pmid: 19605037
references.citation: Neuron. 2001 Feb;29(2):469-84
references.pmid: 11239436
references.citation: Neuroreport. 1994 Dec 30;6(1):21-5
references.pmid: 7703418
references.citation: Science. 1993 Oct 29;262(5134):754-7
references.pmid: 7901909
references.citation: Biophys J. 1999 Feb;76(2):670-8
references.pmid: 9929472
references.citation: Neuroscience. 1995 Feb;64(3):653-64
references.pmid: 7715778
references.citation: J Neurosci Methods. 2004 Apr 30;134(2):179-90
references.pmid: 15003384
references.citation: J Neurosci Methods. 2001 Sep 30;110(1-2):17-24
references.pmid: 11564520
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8074-7
references.pmid: 7644540
references.citation: J Am Chem Soc. 2005 Feb 9;127(5):1340-1
references.pmid: 15686343
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):21-6
references.pmid: 16373512
references.citation: J Neurosci. 1993 Aug;13(8):3394-405
references.pmid: 7688038
references.citation: Neurosci Res. 2001 Oct;41(2):161-83
references.pmid: 11591444