Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays

Multielectrode arrays (MEAs) are extensively used for electrophysiological studies on brain slices, but the spatial resolution and field of recording of conventional arrays are limited by the low number of electrodes available. Here, we present a large-scale array recording simultaneously from 4096 electrodes used to study propagating spontaneous and evoked network activity in acute murine cortico-hippocampal brain slices at unprecedented spatial and temporal resolution. We demonstrate that multiple chemically induced epileptiform episodes in the mouse cortex and hippocampus can be classified according to their spatio-temporal dynamics. Additionally, the large-scale and high-density features of our recording system enable the topological localization and quantification of the effects of antiepileptic drugs in local neuronal microcircuits, based on the distinct field potential propagation patterns. This novel high-resolution approach paves the way to detailed electrophysiological studies in brain circuits spanning spatial scales from single neurons up to the entire slice network.

[1]  C. Koch,et al.  The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes , 2012, Nature Reviews Neuroscience.

[2]  J. Jefferys,et al.  Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. , 1995, Physiological reviews.

[3]  M Gandolfo,et al.  Tracking burst patterns in hippocampal cultures with high-density CMOS-MEAs , 2010, Journal of neural engineering.

[4]  D. McCormick,et al.  On the cellular and network bases of epileptic seizures. , 2001, Annual review of physiology.

[5]  A. Aertsen,et al.  Two-dimensional monitoring of spiking networks in acute brain slices , 2001, Experimental Brain Research.

[6]  Brian Litt,et al.  Flexible, Foldable, Actively Multiplexed, High-Density Electrode Array for Mapping Brain Activity in vivo , 2011, Nature Neuroscience.

[7]  Timothy A. Machado,et al.  Functional connectivity in the retina at the resolution of photoreceptors , 2010, Nature.

[8]  Giuseppe Biagini,et al.  Limbic network interactions leading to hyperexcitability in a model of temporal lobe epilepsy. , 2002, Journal of neurophysiology.

[9]  D. McCormick,et al.  Endogenous Electric Fields May Guide Neocortical Network Activity , 2010, Neuron.

[10]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[11]  D. Johnston,et al.  4-Aminopyridine produces epileptiform activity in hippocampus and enhances synaptic excitation and inhibition. , 1987, Journal of neurophysiology.

[12]  György Buzsáki,et al.  Neural Syntax: Cell Assemblies, Synapsembles, and Readers , 2010, Neuron.

[13]  Rui Xu,et al.  Survey of clustering algorithms , 2005, IEEE Transactions on Neural Networks.

[14]  E. Ferrea,et al.  Cortico-hippocampal hyperexcitability in synapsin I/II/III knockout mice: age-dependency and response to the antiepileptic drug levetiracetam , 2010, Neuroscience.

[15]  G Lynch,et al.  Origins and Distribution of Cholinergically Induced β Rhythms in Hippocampal Slices , 2000, The Journal of Neuroscience.

[16]  G. Buzsáki,et al.  Operational Dynamics in the Hippocampal-entorhinal Axis , 1998, Neuroscience & Biobehavioral Reviews.

[17]  Monya Baker,et al.  From promising to practical: tools to study networks of neurons , 2010, Nature Methods.

[18]  M. Curtis,et al.  Interictal spikes in focal epileptogenesis , 2001, Progress in Neurobiology.

[19]  M. Avoli,et al.  4-aminopyridine-induced epileptiform activity and a GABA-mediated long- lasting depolarization in the rat hippocampus , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  Edward O. Mann,et al.  Which GABAA Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus? , 2008, The Journal of Neuroscience.

[21]  Amiram Grinvald,et al.  VSDI: a new era in functional imaging of cortical dynamics , 2004, Nature Reviews Neuroscience.

[22]  R. Miles,et al.  Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy , 2011, Nature Neuroscience.

[23]  Luca Berdondini,et al.  Active pixel sensor array for high spatio-temporal resolution electrophysiological recordings from single cell to large scale neuronal networks. , 2009, Lab on a chip.

[24]  D M Durand,et al.  Propagation of non‐synaptic epileptiform activity across a lesion in rat hippocampal slices , 2001, The Journal of physiology.

[25]  U. Frey,et al.  Microelectronic system for high-resolution mapping of extracellular electric fields applied to brain slices. , 2009, Biosensors & bioelectronics.

[26]  M. Avoli,et al.  Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro , 2002, Progress in Neurobiology.

[27]  M. Avoli,et al.  CA3-Driven Hippocampal-Entorhinal Loop Controls Rather than Sustains In Vitro Limbic Seizures , 1997, The Journal of Neuroscience.

[28]  R. Miles,et al.  On the Origin of Interictal Activity in Human Temporal Lobe Epilepsy in Vitro , 2002, Science.

[29]  M. Avoli,et al.  The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array , 2011, Neuropharmacology.

[30]  A. Lambacher,et al.  High-resolution multitransistor array recording of electrical field potentials in cultured brain slices. , 2006, Journal of neurophysiology.

[31]  Massimo Avoli,et al.  Epileptiform discharges and a synchronous GABAergic potential induced by 4-aminopyridine in the rat immature hippocampus , 1990, Neuroscience Letters.

[32]  Benjamin J. Whalley,et al.  Development of multi-electrode array screening for anticonvulsants in acute rat brain slices , 2010, Journal of Neuroscience Methods.

[33]  D. Kullmann,et al.  GABA uptake regulates cortical excitability via cell type–specific tonic inhibition , 2003, Nature Neuroscience.

[34]  A Lücke,et al.  Synchronous GABA-Mediated Potentials and Epileptiform Discharges in the Rat Limbic System In Vitro , 1996, The Journal of Neuroscience.

[35]  M. Avoli,et al.  GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity , 2011, Progress in Neurobiology.

[36]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[37]  C. Nicholson,et al.  Theory of current source-density analysis and determination of conductivity tensor for anuran cerebellum. , 1975, Journal of neurophysiology.

[38]  Paolo Massobrio,et al.  A novel algorithm for precise identification of spikes in extracellularly recorded neuronal signals , 2009, Journal of Neuroscience Methods.

[39]  Yannick Bornat,et al.  Large-Scale, High-Resolution Data Acquisition System for Extracellular Recording of Electrophysiological Activity , 2008, IEEE Transactions on Biomedical Engineering.

[40]  D. Kullmann,et al.  Multiple and Plastic Receptors Mediate Tonic GABAA Receptor Currents in the Hippocampus , 2005, The Journal of Neuroscience.

[41]  U. Frey,et al.  Single-chip microelectronic system to interface with living cells. , 2007, Biosensors & bioelectronics.

[42]  Fabrice Wendling,et al.  Mechanisms of physiological and epileptic HFO generation , 2012, Progress in Neurobiology.

[43]  U. Mitzdorf.  Current source-density method and application in cat cerebral cortex: investigation of evoked potentials and EEG phenomena. , 1985, Physiological reviews.

[44]  Nicolas Brunel,et al.  Sensory neural codes using multiplexed temporal scales , 2010, Trends in Neurosciences.