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      Revealing neuronal function through microelectrode array recordings

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          Abstract

          Microelectrode arrays and microprobes have been widely utilized to measure neuronal activity, both in vitro and in vivo. The key advantage is the capability to record and stimulate neurons at multiple sites simultaneously. However, unlike the single-cell or single-channel resolution of intracellular recording, microelectrodes detect signals from all possible sources around every sensor. Here, we review the current understanding of microelectrode signals and the techniques for analyzing them. We introduce the ongoing advancements in microelectrode technology, with focus on achieving higher resolution and quality of recordings by means of monolithic integration with on-chip circuitry. We show how recent advanced microelectrode array measurement methods facilitate the understanding of single neurons as well as network function.

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          Most cited references219

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          Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering.

          This study introduces a new method for detecting and sorting spikes from multiunit recordings. The method combines the wavelet transform, which localizes distinctive spike features, with superparamagnetic clustering, which allows automatic classification of the data without assumptions such as low variance or gaussian distributions. Moreover, an improved method for setting amplitude thresholds for spike detection is proposed. We describe several criteria for implementation that render the algorithm unsupervised and fast. The algorithm is compared to other conventional methods using several simulated data sets whose characteristics closely resemble those of in vivo recordings. For these data sets, we found that the proposed algorithm outperformed conventional methods.
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            Electrical stimulation of excitable tissue: design of efficacious and safe protocols.

            The physical basis for electrical stimulation of excitable tissue, as used by electrophysiological researchers and clinicians in functional electrical stimulation, is presented with emphasis on the fundamental mechanisms of charge injection at the electrode/tissue interface. Faradaic and non-Faradaic charge transfer mechanisms are presented and contrasted. An electrical model of the electrode/tissue interface is given. The physical basis for the origin of electrode potentials is given. Various methods of controlling charge delivery during pulsing are presented. Electrochemical reversibility is discussed. Commonly used electrode materials and stimulation protocols are reviewed in terms of stimulation efficacy and safety. Principles of stimulation of excitable tissue are reviewed with emphasis on efficacy and safety. Mechanisms of damage to tissue and the electrode are reviewed.
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              Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements.

              Simultaneous recording from large numbers of neurons is a prerequisite for understanding their cooperative behavior. Various recording techniques and spike separation methods are being used toward this goal. However, the error rates involved in spike separation have not yet been quantified. We studied the separation reliability of "tetrode" (4-wire electrode)-recorded spikes by monitoring simultaneously from the same cell intracellularly with a glass pipette and extracellularly with a tetrode. With manual spike sorting, we found a trade-off between Type I and Type II errors, with errors typically ranging from 0 to 30% depending on the amplitude and firing pattern of the cell, the similarity of the waveshapes of neighboring neurons, and the experience of the operator. Performance using only a single wire was markedly lower, indicating the advantages of multiple-site monitoring techniques over single-wire recordings. For tetrode recordings, error rates were increased by burst activity and during periods of cellular synchrony. The lowest possible separation error rates were estimated by a search for the best ellipsoidal cluster shape. Human operator performance was significantly below the estimated optimum. Investigation of error distributions indicated that suboptimal performance was caused by inability of the operators to mark cluster boundaries accurately in a high-dimensional feature space. We therefore hypothesized that automatic spike-sorting algorithms have the potential to significantly lower error rates. Implementation of a semi-automatic classification system confirms this suggestion, reducing errors close to the estimated optimum, in the range 0-8%.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                06 January 2015
                2014
                : 8
                : 423
                Affiliations
                [1] 1RIKEN Quantitative Biology Center, RIKEN Kobe, Japan
                [2] 2Graduate School of Frontier Biosciences, Osaka University Osaka, Japan
                [3] 3Department of Biosystems Science and Engineering, ETH Zurich Basel, Switzerland
                Author notes

                Edited by: Noriko Hiroi, Keio University, Japan

                Reviewed by: Ahmed El Hady, Princeton University/HHMI, USA; Yoonkey Nam, Korea Advanced Institute of Science and Technology, Korea (South)

                *Correspondence: Marie Engelene J. Obien, Frey Initiative Research Unit, RIKEN Quantitative Biology Center, RIKEN, Minatojima-minamimachi 2-2-3 Chuo-ku, Kobe, Hyogo 650-0047 Japan e-mail: meobien@ 123456riken.jp

                This article was submitted to Systems Biology, a section of the journal Frontiers in Neuroscience.

                Article
                10.3389/fnins.2014.00423
                4285113
                25610364
                cb22190c-10ec-4b30-b386-243c63ab80a9
                Copyright © 2015 Obien, Deligkaris, Bullmann, Bakkum and Frey.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 October 2014
                : 03 December 2014
                Page count
                Figures: 14, Tables: 0, Equations: 3, References: 277, Pages: 30, Words: 23299
                Categories
                Physiology
                Review Article

                Neurosciences
                microelectrode array,neuronal function,extracellular recording,stimulation,cmos,multielectrode array,neuron-electrode interface,multi-scale modeling

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