A microfluidic microelectrode array for simultaneous electrophysiology, chemical stimulation, and imaging of brain slices.

In order to understand information processing in neural circuits, it is necessary to detect both electrical and chemical signaling with high spatial and temporal resolution. Although the primary currency of neural information processing is electrical, many of the downstream effects of the electrical signals on the circuits that generate them are dependent on activity-dependent increases in intracellular calcium concentration. It is therefore of great utility to be able to record electrical signals in neural circuits at multiple sites, while at the same time detecting optical signals from reporters of intracellular calcium levels. We describe here a microfluidic multi-electrode array (MMEA) capable of high-resolution extracellular recording from brain slices that is optically compatible with calcium imaging at single cell resolution. We show the application of the MMEA device to record waves of spontaneous activity in developing cortical slices and to perform multi-site extracellular recordings during simultaneous calcium imaging of activity. The MMEA has the unique capability to simultaneously allow focal electrical and chemical stimuli at different locations of the surface of a brain slice.

[1]  William J Moody,et al.  Ion channel development, spontaneous activity, and activity-dependent development in nerve and muscle cells. , 2005, Physiological reviews.

[2]  William J Moody,et al.  Bilaterally propagating waves of spontaneous activity arising from discrete pacemakers in the neonatal mouse cerebral cortex , 2009, Developmental neurobiology.

[3]  Miguel A. L. Nicolelis,et al.  Brain–machine interfaces: past, present and future , 2006, Trends in Neurosciences.

[4]  Jichul Kim,et al.  Development and characterization of a microfluidic chamber incorporating fluid ports with active suction for localized chemical stimulation of brain slices. , 2011, Lab on a chip.

[5]  Javeed Shaikh Mohammed,et al.  Microfluidic add-on for standard electrophysiology chambers. , 2008, Lab on a chip.

[6]  G. Deuschl,et al.  Subthalamic nucleus deep brain stimulation: Summary and meta‐analysis of outcomes , 2006, Movement disorders : official journal of the Movement Disorder Society.

[7]  Yu Huang,et al.  Brain slice on a chip: opportunities and challenges of applying microfluidic technology to intact tissues. , 2012, Lab on a chip.

[8]  R. Pearce,et al.  A microfluidic brain slice perfusion chamber for multisite recording using penetrating electrodes , 2010, Journal of Neuroscience Methods.

[9]  G. Deuschl,et al.  A randomized trial of deep-brain stimulation for Parkinson's disease. , 2006, The New England journal of medicine.

[10]  Jerry Silver,et al.  Atlas of the Prenatal Mouse Brain , 1991 .

[11]  William J Moody,et al.  Roles of glutamate and GABA receptors in setting the developmental timing of spontaneous synchronized activity in the developing mouse cortex , 2007, Developmental neurobiology.

[12]  S. Soper,et al.  Simple room temperature bonding of thermoplastics and poly(dimethylsiloxane). , 2011, Lab on a chip.

[13]  S. Cogan Neural stimulation and recording electrodes. , 2008, Annual review of biomedical engineering.

[14]  Karl Deisseroth,et al.  Optetrode: a multichannel readout for optogenetic control in freely moving mice , 2011, Nature Neuroscience.

[15]  William J Moody,et al.  The self‐regulating nature of spontaneous synchronized activity in developing mouse cortical neurones , 2006, The Journal of physiology.

[16]  Lief E. Fenno,et al.  Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins , 2011, Nature Methods.

[17]  Amir M. Sodagar,et al.  Microelectrodes, Microelectronics, and Implantable Neural Microsystems , 2008, Proceedings of the IEEE.

[18]  Andreas Möller,et al.  On Micro-Electrode Array Revival: Its Development, Sophistication of Recording, and Stimulation , 2006 .

[19]  R. Wightman,et al.  Microelectrodes for studying neurobiology. , 2008, Current opinion in chemical biology.

[20]  Justin C. Williams,et al.  Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment. , 2007, Lab on a chip.

[21]  Fred J. Sigworth,et al.  An air-molding technique for fabricating PDMS planar patch-clamp electrodes , 2004, Pflügers Archiv.

[22]  C. McIntyre,et al.  Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both , 2004, Clinical Neurophysiology.

[23]  Albert Folch,et al.  A high-performance elastomeric patch clamp chip. , 2006, Lab on a chip.

[24]  Nicholas G Hatsopoulos,et al.  The science of neural interface systems. , 2009, Annual review of neuroscience.

[25]  William J. Moody,et al.  Bimodal septal and cortical triggering and complex propagation patterns of spontaneous waves of activity in the developing mouse cerebral cortex , 2010, Developmental neurobiology.

[26]  David Juncker,et al.  Chamber and microfluidic probe for microperfusion of organotypic brain slices. , 2010, Lab on a chip.

[27]  Luke P. Lee,et al.  Open-access microfluidic patch-clamp array with raised lateral cell trapping sites. , 2006, Lab on a chip.

[28]  Dae-Hyeong Kim,et al.  Flexible and stretchable electronics for biointegrated devices. , 2012, Annual review of biomedical engineering.

[29]  Malcolm Lidierth,et al.  sigTOOL: A MATLAB-based environment for sharing laboratory-developed software to analyze biological signals , 2009, Journal of Neuroscience Methods.