Abstract
Comparability of responses to neuroactive compounds and spatially and temporally resolved delivery of soluble factors are two major key features for pharmacological assays. Here, we describe the fabrication and the use of a device for long-term growth of twin neuronal networks and for their controlled biochemical stimulation. The device is formed by a PDMS microfluidic chamber coupled to a flat Microelectrode Array (MEA), which provides the electrophysiological readout of the pharmacological stimulation. A partial physical barrier divides the chamber in two sub-compartments, where two functionally independent but fluidically connected neuronal networks can be grown. This platform improves biological comparability between cultures and allows to perform selective and temporally controlled stimulations to neurons, running parallel pharmacological tests on the same device.
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References
Chiappalone M, Vato A, Tedesco M et al (2003) Networks of neurons coupled to microelectrode arrays: a neuronal sensory system for pharmacological applications. Biosens Bioelectron 18:627–634
Morin FO, Takamura Y, Tamiya E (2005) Investigating neuronal activity with planar microelectrode arrays: achievements and new perspectives. J Biosci Bioeng 100:131–143
Boehler MD, Wheeler BC, Brewer GJ (2007) Added astroglia promote greater synapse density and higher activity in neuronal networks. Neuron Glia Biol 3:127–140
Chen Y, Guo C, Lim L et al (2008) Compact microelectrode array system: tool for in situ monitoring of drug effects on neurotransmitter release from neural cells. Anal Chem 80:1133–1140
Johnstone AF, Gross GW, Weiss DG et al (2010) Microelectrode arrays: a physiologically based neurotoxicity testing platform for the 21st century. Neurotoxicology 31:331–350
Mourzina Y, Kaliaguine D, Schulte P et al (2006) Patterning chemical stimulation of reconstructed neuronal networks. Anal Chim Acta 575:281–289
Sung JH, Kam C, Shuler ML (2010) A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10:446–455
Taylor AM, Jeon NL (2010) Micro-scale and microfluidic devices for neurobiology. Curr Opin Neurobiol 20:640–647
Shi P, Nedelec S, Wichterle H et al (2010) Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding. Lab Chip 10:1005–1010
Wang J, Ren L, Li L et al (2009) Microfluidics: a new cosset for neurobiology. Lab Chip 9:644–652
Biffi E, Piraino F, Pedrocchi A et al (2012) A microfluidic platform for controlled biochemical stimulation of twin neuronal networks. Biomicrofluidics 6:24106–2410610
Biffi E, Regalia G, Menegon A et al (2013) The influence of neuronal density and maturation on network activity of hippocampal cell cultures: a methodological study. PLoS One 8:e83899. doi:10.1371/journal.pone.0083899
Acknowledgements
The author would like to thank Dr. Andrea Menegon, Dr. Luca Muzio and Dr. Roberta De Ceglia for their help in neuronal culture preparation. This study was partially supported by Fondazione Cariplo, grant no. 2008-2531, and by the “Biosensors and artificial bio-systems” convention between the Italian Institute of Technology and Politecnico di Milano.
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Regalia, G., Biffi, E., Rasponi, M., Pedrocchi, A. (2015). Selective Biochemical Manipulation of Twin Neuronal Networks on Microelectrode Arrays. In: Biffi, E. (eds) Microfluidic and Compartmentalized Platforms for Neurobiological Research. Neuromethods, vol 103. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2510-0_13
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DOI: https://doi.org/10.1007/978-1-4939-2510-0_13
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